EP0636614A1 - Dérivés de 1-benzènesulfonyl-1,3-dihydro-2H-benzimidazol-2-one, leur préparation, les compositions pharmaceutiques en contenant - Google Patents
Dérivés de 1-benzènesulfonyl-1,3-dihydro-2H-benzimidazol-2-one, leur préparation, les compositions pharmaceutiques en contenant Download PDFInfo
- Publication number
- EP0636614A1 EP0636614A1 EP94401736A EP94401736A EP0636614A1 EP 0636614 A1 EP0636614 A1 EP 0636614A1 EP 94401736 A EP94401736 A EP 94401736A EP 94401736 A EP94401736 A EP 94401736A EP 0636614 A1 EP0636614 A1 EP 0636614A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- group
- alkyl
- amino
- substituted
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 81
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
- BPTIOJPNCPTPDO-UHFFFAOYSA-N 3-(benzenesulfonyl)-1h-benzimidazol-2-one Chemical class O=C1NC2=CC=CC=C2N1S(=O)(=O)C1=CC=CC=C1 BPTIOJPNCPTPDO-UHFFFAOYSA-N 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 447
- -1 formyloxy Chemical group 0.000 claims description 168
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 105
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 94
- 238000000034 method Methods 0.000 claims description 82
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
- 125000003545 alkoxy group Chemical group 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 41
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 37
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 32
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 31
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 30
- 125000001424 substituent group Chemical group 0.000 claims description 28
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 27
- 125000003277 amino group Chemical group 0.000 claims description 26
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 26
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 20
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 18
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 17
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 17
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 12
- 102000004136 Vasopressin Receptors Human genes 0.000 claims description 11
- 108090000643 Vasopressin Receptors Proteins 0.000 claims description 11
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 11
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- 239000002243 precursor Substances 0.000 claims description 9
- RHYBFKMFHLPQPH-UHFFFAOYSA-N N-methylhydantoin Chemical compound CN1CC(=O)NC1=O RHYBFKMFHLPQPH-UHFFFAOYSA-N 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 7
- 125000001475 halogen functional group Chemical group 0.000 claims description 7
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 6
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 6
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000006384 methylpyridyl group Chemical group 0.000 claims description 6
- 239000002464 receptor antagonist Substances 0.000 claims description 6
- 229940044551 receptor antagonist Drugs 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 5
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 5
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 5
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- 125000001425 triazolyl group Chemical group 0.000 claims description 5
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 4
- 230000009466 transformation Effects 0.000 claims description 4
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
- 125000005596 alkyl carboxamido group Chemical group 0.000 claims description 3
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 3
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 3
- 229940091173 hydantoin Drugs 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000005485 noradamantyl group Chemical group 0.000 claims description 2
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 2
- 239000003336 oxytocin antagonist Substances 0.000 claims description 2
- 229940121361 oxytocin antagonists Drugs 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 abstract description 18
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 abstract description 14
- 229960003726 vasopressin Drugs 0.000 abstract description 14
- 108010004977 Vasopressins Proteins 0.000 abstract description 11
- 102000002852 Vasopressins Human genes 0.000 abstract description 11
- 101800000989 Oxytocin Proteins 0.000 abstract description 7
- 102400000050 Oxytocin Human genes 0.000 abstract description 7
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 abstract description 7
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 abstract description 6
- 229960001723 oxytocin Drugs 0.000 abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 400
- 239000000203 mixture Substances 0.000 description 387
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 318
- 239000000047 product Substances 0.000 description 270
- 239000000243 solution Substances 0.000 description 233
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 223
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 217
- 229910001868 water Inorganic materials 0.000 description 214
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 192
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 184
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 169
- 229910052938 sodium sulfate Inorganic materials 0.000 description 169
- 235000011152 sodium sulphate Nutrition 0.000 description 169
- 239000007832 Na2SO4 Substances 0.000 description 147
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 144
- 239000002904 solvent Substances 0.000 description 139
- 238000010992 reflux Methods 0.000 description 133
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 101
- 238000003756 stirring Methods 0.000 description 91
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 90
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 88
- 239000000377 silicon dioxide Substances 0.000 description 86
- 239000011734 sodium Substances 0.000 description 81
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 80
- 229910052708 sodium Inorganic materials 0.000 description 80
- 238000002425 crystallisation Methods 0.000 description 73
- 230000008025 crystallization Effects 0.000 description 73
- 239000011541 reaction mixture Substances 0.000 description 72
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 61
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 56
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 47
- 239000003921 oil Substances 0.000 description 46
- 235000019198 oils Nutrition 0.000 description 46
- 239000002244 precipitate Substances 0.000 description 44
- 239000000706 filtrate Substances 0.000 description 43
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 42
- QVQSOXMXXFZAKU-UHFFFAOYSA-N 4-chloro-1,2-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1[N+]([O-])=O QVQSOXMXXFZAKU-UHFFFAOYSA-N 0.000 description 40
- 230000009471 action Effects 0.000 description 39
- 239000003054 catalyst Substances 0.000 description 35
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 34
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 33
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 32
- 238000013019 agitation Methods 0.000 description 31
- XGLVDUUYFKXKPL-UHFFFAOYSA-N 2-(2-methoxyethoxy)-n,n-bis[2-(2-methoxyethoxy)ethyl]ethanamine Chemical compound COCCOCCN(CCOCCOC)CCOCCOC XGLVDUUYFKXKPL-UHFFFAOYSA-N 0.000 description 26
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 22
- 229910052763 palladium Inorganic materials 0.000 description 22
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 20
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 19
- 238000004587 chromatography analysis Methods 0.000 description 19
- 239000012429 reaction media Substances 0.000 description 19
- 239000012312 sodium hydride Substances 0.000 description 19
- 229910000104 sodium hydride Inorganic materials 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 238000001816 cooling Methods 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 16
- 238000005984 hydrogenation reaction Methods 0.000 description 16
- 229910052759 nickel Inorganic materials 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- MYONAGGJKCJOBT-UHFFFAOYSA-N benzimidazol-2-one Chemical class C1=CC=CC2=NC(=O)N=C21 MYONAGGJKCJOBT-UHFFFAOYSA-N 0.000 description 15
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 239000000470 constituent Substances 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 11
- UOHMMEJUHBCKEE-UHFFFAOYSA-N prehnitene Chemical compound CC1=CC=C(C)C(C)=C1C UOHMMEJUHBCKEE-UHFFFAOYSA-N 0.000 description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 10
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 10
- 239000008188 pellet Substances 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 150000003254 radicals Chemical class 0.000 description 10
- QECYXMKYZQXEHM-UHFFFAOYSA-N 2-methoxy-4-nitrobenzenesulfonyl chloride Chemical compound COC1=CC([N+]([O-])=O)=CC=C1S(Cl)(=O)=O QECYXMKYZQXEHM-UHFFFAOYSA-N 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 9
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 8
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- QUIMTLZDMCNYGY-UHFFFAOYSA-N 2,4-dichloro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1Cl QUIMTLZDMCNYGY-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 6
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 150000004820 halides Chemical class 0.000 description 6
- 239000002198 insoluble material Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- PUJYXVAATTZGRU-UHFFFAOYSA-N methyl 4-chlorosulfonyl-3-methoxybenzoate Chemical compound COC(=O)C1=CC=C(S(Cl)(=O)=O)C(OC)=C1 PUJYXVAATTZGRU-UHFFFAOYSA-N 0.000 description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- GELMWIVBBPAMIO-UHFFFAOYSA-N 2-methylbutan-2-amine Chemical compound CCC(C)(C)N GELMWIVBBPAMIO-UHFFFAOYSA-N 0.000 description 5
- KWVHCMXSQWZHGG-UHFFFAOYSA-N 3-cyclohexyl-5-ethoxy-1h-benzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2NC(=O)N1C1CCCCC1 KWVHCMXSQWZHGG-UHFFFAOYSA-N 0.000 description 5
- CQMLFUYGWQJYHM-UHFFFAOYSA-N 5-chloro-3-cyclohexyl-1h-benzimidazol-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)N1C1CCCCC1 CQMLFUYGWQJYHM-UHFFFAOYSA-N 0.000 description 5
- YFROLUWVMXHYEL-UHFFFAOYSA-N 5-ethoxy-3-pyridin-2-yl-1h-benzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2NC(=O)N1C1=CC=CC=N1 YFROLUWVMXHYEL-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 102000004279 Oxytocin receptors Human genes 0.000 description 5
- 108090000876 Oxytocin receptors Proteins 0.000 description 5
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 5
- 150000001448 anilines Chemical group 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 229940093475 2-ethoxyethanol Drugs 0.000 description 4
- WYBYBYODUPZYPE-UHFFFAOYSA-N 3-(1-adamantyl)-5-ethoxy-1h-benzimidazol-2-one Chemical compound C1C(C2)CC(C3)CC2CC13N1C(=O)NC2=CC=C(OCC)C=C21 WYBYBYODUPZYPE-UHFFFAOYSA-N 0.000 description 4
- GNPNHMQCKJAPRR-UHFFFAOYSA-N 3-[2-[di(propan-2-yl)amino]ethyl]-5-ethoxy-1h-benzimidazol-2-one Chemical compound CCOC1=CC=C2NC(=O)N(CCN(C(C)C)C(C)C)C2=C1 GNPNHMQCKJAPRR-UHFFFAOYSA-N 0.000 description 4
- KQWRXKLKOQUHMU-UHFFFAOYSA-N 3-cycloheptyl-5-ethoxy-1h-benzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2NC(=O)N1C1CCCCCC1 KQWRXKLKOQUHMU-UHFFFAOYSA-N 0.000 description 4
- UQUPGDHPONCBDL-UHFFFAOYSA-N 3-cyclohexyl-5-(2-methoxyethoxy)-1h-benzimidazol-2-one Chemical compound C12=CC(OCCOC)=CC=C2NC(=O)N1C1CCCCC1 UQUPGDHPONCBDL-UHFFFAOYSA-N 0.000 description 4
- RZCFNXRMXWEVKJ-UHFFFAOYSA-N 3-cyclohexyl-5-cyclopentyloxy-1h-benzimidazol-2-one Chemical compound C1=C2N(C3CCCCC3)C(=O)NC2=CC=C1OC1CCCC1 RZCFNXRMXWEVKJ-UHFFFAOYSA-N 0.000 description 4
- SECDLJDPSVFNRP-UHFFFAOYSA-N 3-cyclohexyl-5-methoxy-1h-benzimidazol-2-one Chemical compound C12=CC(OC)=CC=C2NC(=O)N1C1CCCCC1 SECDLJDPSVFNRP-UHFFFAOYSA-N 0.000 description 4
- VJGRBHHOJDVXGT-UHFFFAOYSA-N 5-chloro-3-(2-chlorophenyl)-1h-benzimidazol-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)N1C1=CC=CC=C1Cl VJGRBHHOJDVXGT-UHFFFAOYSA-N 0.000 description 4
- YBZAEXBYULOETF-UHFFFAOYSA-N 5-chloro-3-cycloheptyl-1h-benzimidazol-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)N1C1CCCCCC1 YBZAEXBYULOETF-UHFFFAOYSA-N 0.000 description 4
- LCINIZFGLQWIJN-UHFFFAOYSA-N 5-chloro-n-cyclohexyl-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NC1CCCCC1 LCINIZFGLQWIJN-UHFFFAOYSA-N 0.000 description 4
- KWNBDEVOONGXOC-UHFFFAOYSA-N 5-ethoxy-3-(1-methoxy-2-methylpropan-2-yl)-1h-benzimidazol-2-one Chemical compound CCOC1=CC=C2NC(=O)N(C(C)(C)COC)C2=C1 KWNBDEVOONGXOC-UHFFFAOYSA-N 0.000 description 4
- YCJUZESZMBJCMY-UHFFFAOYSA-N 5-ethoxy-3-(2,4,4-trimethylpentan-2-yl)-1h-benzimidazol-2-one Chemical compound CCOC1=CC=C2NC(=O)N(C(C)(C)CC(C)(C)C)C2=C1 YCJUZESZMBJCMY-UHFFFAOYSA-N 0.000 description 4
- ULZDATGTSOTKQM-UHFFFAOYSA-N 5-ethoxy-3-(2-morpholin-4-ylethyl)-1h-benzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2NC(=O)N1CCN1CCOCC1 ULZDATGTSOTKQM-UHFFFAOYSA-N 0.000 description 4
- HIYRLIYHBCRBGQ-UHFFFAOYSA-N 5-ethoxy-3-(oxan-4-yl)-1h-benzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2NC(=O)N1C1CCOCC1 HIYRLIYHBCRBGQ-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 101800001144 Arg-vasopressin Proteins 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- 239000004202 carbamide Substances 0.000 description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 4
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- FQDIANVAWVHZIR-UPHRSURJSA-N (z)-1,4-dichlorobut-2-ene Chemical compound ClC\C=C/CCl FQDIANVAWVHZIR-UPHRSURJSA-N 0.000 description 3
- QIJIUJYANDSEKG-UHFFFAOYSA-N 2,4,4-trimethylpentan-2-amine Chemical compound CC(C)(C)CC(C)(C)N QIJIUJYANDSEKG-UHFFFAOYSA-N 0.000 description 3
- DJIMRESXGZQJBT-UHFFFAOYSA-N 3-(1-benzylpiperidin-4-yl)-5-chloro-1h-benzimidazol-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)N1C(CC1)CCN1CC1=CC=CC=C1 DJIMRESXGZQJBT-UHFFFAOYSA-N 0.000 description 3
- RWTWLVAENZMLHB-UHFFFAOYSA-N 3-(2,3-dihydro-1h-inden-2-yl)-5-ethoxy-1h-benzimidazol-2-one Chemical compound C1C2=CC=CC=C2CC1N1C(=O)NC2=CC=C(OCC)C=C21 RWTWLVAENZMLHB-UHFFFAOYSA-N 0.000 description 3
- BJTQCVLXICMUMZ-UHFFFAOYSA-N 3-(2-chlorophenyl)-5-ethoxy-1h-benzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2NC(=O)N1C1=CC=CC=C1Cl BJTQCVLXICMUMZ-UHFFFAOYSA-N 0.000 description 3
- DJJVQLXTBOLTDB-UHFFFAOYSA-N 3-cyclopentyl-5-ethoxy-1h-benzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2NC(=O)N1C1CCCC1 DJJVQLXTBOLTDB-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- OARTUDLHQLLYAA-UHFFFAOYSA-N 5-chloro-3-(3-chlorophenyl)-1h-benzimidazol-2-one Chemical compound ClC1=CC=CC(N2C(NC3=CC=C(Cl)C=C32)=O)=C1 OARTUDLHQLLYAA-UHFFFAOYSA-N 0.000 description 3
- MCNHWLILAIRSOX-UHFFFAOYSA-N 5-chloro-3-(cyclohexylmethyl)-1h-benzimidazol-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)N1CC1CCCCC1 MCNHWLILAIRSOX-UHFFFAOYSA-N 0.000 description 3
- UCBSMOSFCAQPAI-UHFFFAOYSA-N 5-chloro-3-phenyl-1h-benzimidazol-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)N1C1=CC=CC=C1 UCBSMOSFCAQPAI-UHFFFAOYSA-N 0.000 description 3
- XBPZUFAPYXVCCK-UHFFFAOYSA-N 5-ethoxy-3-(4-methoxyphenyl)-1h-benzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2NC(=O)N1C1=CC=C(OC)C=C1 XBPZUFAPYXVCCK-UHFFFAOYSA-N 0.000 description 3
- CQKMHYPMJQSFNA-UHFFFAOYSA-N 5-ethoxy-3-(4-methylpiperazin-1-yl)-1h-benzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2NC(=O)N1N1CCN(C)CC1 CQKMHYPMJQSFNA-UHFFFAOYSA-N 0.000 description 3
- MDQCARPBUSHAGP-UHFFFAOYSA-N 5-ethoxy-3-(4-propan-2-ylphenyl)-1h-benzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2NC(=O)N1C1=CC=C(C(C)C)C=C1 MDQCARPBUSHAGP-UHFFFAOYSA-N 0.000 description 3
- KEPJNRWTMFHUCH-UHFFFAOYSA-N 5-ethoxy-3-morpholin-4-yl-1h-benzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2NC(=O)N1N1CCOCC1 KEPJNRWTMFHUCH-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 3
- HIGRAKVNKLCVCA-UHFFFAOYSA-N alumine Chemical compound C1=CC=[Al]C=C1 HIGRAKVNKLCVCA-UHFFFAOYSA-N 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 150000008641 benzimidazolones Chemical class 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229910052987 metal hydride Inorganic materials 0.000 description 3
- 150000004681 metal hydrides Chemical class 0.000 description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 3
- 150000002828 nitro derivatives Chemical class 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000009329 sexual behaviour Effects 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 2
- AMSIAIRQIAPAPM-UHFFFAOYSA-N 1-(2-methoxyethoxy)-4-nitrobenzene Chemical compound COCCOC1=CC=C([N+]([O-])=O)C=C1 AMSIAIRQIAPAPM-UHFFFAOYSA-N 0.000 description 2
- ZNBDTVJWJZTDLU-UHFFFAOYSA-N 1-(4-amino-2-methoxyphenyl)sulfonyl-3-cyclohexyl-5-ethoxybenzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(N)=CC=2)OC)C(=O)N1C1CCCCC1 ZNBDTVJWJZTDLU-UHFFFAOYSA-N 0.000 description 2
- KZVVWTCSNMUVRF-UHFFFAOYSA-N 1-benzyl-n-(5-chloro-2-nitrophenyl)piperidin-4-amine Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NC1CCN(CC=2C=CC=CC=2)CC1 KZVVWTCSNMUVRF-UHFFFAOYSA-N 0.000 description 2
- YUBDLZGUSSWQSS-UHFFFAOYSA-N 1-benzylpiperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=CC=C1 YUBDLZGUSSWQSS-UHFFFAOYSA-N 0.000 description 2
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 2
- XEHNLVMHWYPNEQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-2-amine;hydron;chloride Chemical compound Cl.C1=CC=C2CC(N)CC2=C1 XEHNLVMHWYPNEQ-UHFFFAOYSA-N 0.000 description 2
- AYGZKRRIULCJKC-UHFFFAOYSA-N 2,4-dimethoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C(OC)=C1 AYGZKRRIULCJKC-UHFFFAOYSA-N 0.000 description 2
- QFLNZIHUAICVQA-UHFFFAOYSA-N 2-(5-chloro-2-nitroanilino)-2-methylpropan-1-ol Chemical compound OCC(C)(C)NC1=CC(Cl)=CC=C1[N+]([O-])=O QFLNZIHUAICVQA-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 description 2
- AOQISHZFOXZXJD-UHFFFAOYSA-N 2-n-(1-benzylpiperidin-4-yl)-4-chlorobenzene-1,2-diamine Chemical compound NC1=CC=C(Cl)C=C1NC1CCN(CC=2C=CC=CC=2)CC1 AOQISHZFOXZXJD-UHFFFAOYSA-N 0.000 description 2
- FVPQSPPDDGPFSJ-UHFFFAOYSA-N 2-n-(2-chlorophenyl)-4-ethoxybenzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NC=2C(=CC=CC=2)Cl)=C1 FVPQSPPDDGPFSJ-UHFFFAOYSA-N 0.000 description 2
- VLMBPOYUMCMIFV-UHFFFAOYSA-N 2-n-cycloheptyl-4-ethoxybenzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NC2CCCCCC2)=C1 VLMBPOYUMCMIFV-UHFFFAOYSA-N 0.000 description 2
- IYAYXDKADDZMEH-UHFFFAOYSA-N 2-n-cyclohexyl-4-(2-methoxyethoxy)benzene-1,2-diamine Chemical compound COCCOC1=CC=C(N)C(NC2CCCCC2)=C1 IYAYXDKADDZMEH-UHFFFAOYSA-N 0.000 description 2
- SAPHNRQJBWTCDJ-UHFFFAOYSA-N 2-n-cyclohexyl-4-cyclopentyloxybenzene-1,2-diamine Chemical compound C1=C(NC2CCCCC2)C(N)=CC=C1OC1CCCC1 SAPHNRQJBWTCDJ-UHFFFAOYSA-N 0.000 description 2
- QXJWDRSIGYQUSX-UHFFFAOYSA-N 2-n-cyclohexyl-4-ethoxybenzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NC2CCCCC2)=C1 QXJWDRSIGYQUSX-UHFFFAOYSA-N 0.000 description 2
- XPBBFCWCMWESOK-UHFFFAOYSA-N 2-n-cyclohexyl-4-methoxybenzene-1,2-diamine Chemical compound COC1=CC=C(N)C(NC2CCCCC2)=C1 XPBBFCWCMWESOK-UHFFFAOYSA-N 0.000 description 2
- JVELUFVIJVZXRW-UHFFFAOYSA-N 2-n-cyclopentyl-4-ethoxybenzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NC2CCCC2)=C1 JVELUFVIJVZXRW-UHFFFAOYSA-N 0.000 description 2
- ZQUNQYDHMSJKCJ-UHFFFAOYSA-N 3-[4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]-1,1-diethylurea Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(NC(=O)N(CC)CC)=CC=2)OC)C(=O)N1C1CCCCC1 ZQUNQYDHMSJKCJ-UHFFFAOYSA-N 0.000 description 2
- AACCMSITKGVFIG-UHFFFAOYSA-N 3-[4-(5-chloro-3-cycloheptyl-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]-1,1-diethylurea Chemical compound COC1=CC(NC(=O)N(CC)CC)=CC=C1S(=O)(=O)N1C(=O)N(C2CCCCCC2)C2=CC(Cl)=CC=C21 AACCMSITKGVFIG-UHFFFAOYSA-N 0.000 description 2
- JYOWFJRAALKPBB-UHFFFAOYSA-N 3-[4-(5-chloro-3-cyclohexyl-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]-1,1-diethylurea Chemical compound COC1=CC(NC(=O)N(CC)CC)=CC=C1S(=O)(=O)N1C(=O)N(C2CCCCC2)C2=CC(Cl)=CC=C21 JYOWFJRAALKPBB-UHFFFAOYSA-N 0.000 description 2
- CLZGGSAQMQCSQV-UHFFFAOYSA-N 3-[4-(5-ethoxy-2-oxo-3-pyridin-2-ylbenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]-1,1-diethylurea Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(NC(=O)N(CC)CC)=CC=2)OC)C(=O)N1C1=CC=CC=N1 CLZGGSAQMQCSQV-UHFFFAOYSA-N 0.000 description 2
- LBCPCLJYVWZDRP-UHFFFAOYSA-N 3-[4-[3-(1-adamantyl)-5-ethoxy-2-oxobenzimidazol-1-yl]sulfonyl-3-methoxyphenyl]-1,1-diethylurea Chemical compound O=C1N(C23CC4CC(CC(C4)C2)C3)C2=CC(OCC)=CC=C2N1S(=O)(=O)C1=CC=C(NC(=O)N(CC)CC)C=C1OC LBCPCLJYVWZDRP-UHFFFAOYSA-N 0.000 description 2
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 2
- FAGOUGQTKPEFMF-UHFFFAOYSA-N 3-cyclohexyl-1-[4-(dimethylamino)-2-methoxyphenyl]sulfonyl-5-ethoxybenzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)N(C)C)OC)C(=O)N1C1CCCCC1 FAGOUGQTKPEFMF-UHFFFAOYSA-N 0.000 description 2
- DIOBEQCFVVJJBU-UHFFFAOYSA-N 4-(2-methoxyethoxy)aniline Chemical compound COCCOC1=CC=C(N)C=C1 DIOBEQCFVVJJBU-UHFFFAOYSA-N 0.000 description 2
- RAQBYJLDWOYLBO-UHFFFAOYSA-N 4-(3-cycloheptyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxy-n-(2-methylbutan-2-yl)benzamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)NC(C)(C)CC)OC)C(=O)N1C1CCCCCC1 RAQBYJLDWOYLBO-UHFFFAOYSA-N 0.000 description 2
- QARMBOYCMVAWHL-UHFFFAOYSA-N 4-(3-cyclohexyl-5-cyclopentyloxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxy-n-(2-methylbutan-2-yl)benzamide Chemical compound COC1=CC(C(=O)NC(C)(C)CC)=CC=C1S(=O)(=O)N1C(=O)N(C2CCCCC2)C2=CC(OC3CCCC3)=CC=C21 QARMBOYCMVAWHL-UHFFFAOYSA-N 0.000 description 2
- KSMVBYPXNKCPAJ-UHFFFAOYSA-N 4-Methylcyclohexylamine Chemical compound CC1CCC(N)CC1 KSMVBYPXNKCPAJ-UHFFFAOYSA-N 0.000 description 2
- QQMLOIRXMIGGEY-UHFFFAOYSA-N 4-[3-cyclohexyl-5-(2-methoxyethoxy)-2-oxobenzimidazol-1-yl]sulfonyl-3-methoxy-n-(2-methylbutan-2-yl)benzamide Chemical compound COC1=CC(C(=O)NC(C)(C)CC)=CC=C1S(=O)(=O)N1C(=O)N(C2CCCCC2)C2=CC(OCCOC)=CC=C21 QQMLOIRXMIGGEY-UHFFFAOYSA-N 0.000 description 2
- LFQMDJZFDXWNOY-UHFFFAOYSA-N 4-[5-ethoxy-3-(oxan-4-yl)-2-oxobenzimidazol-1-yl]sulfonyl-3-methoxy-n-(2-methylbutan-2-yl)benzamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)NC(C)(C)CC)OC)C(=O)N1C1CCOCC1 LFQMDJZFDXWNOY-UHFFFAOYSA-N 0.000 description 2
- IMLXLGZJLAOKJN-UHFFFAOYSA-N 4-aminocyclohexan-1-ol Chemical compound NC1CCC(O)CC1 IMLXLGZJLAOKJN-UHFFFAOYSA-N 0.000 description 2
- ISECUHSHBOCFSW-UHFFFAOYSA-N 4-chloro-2-n-(2-chlorophenyl)benzene-1,2-diamine Chemical compound NC1=CC=C(Cl)C=C1NC1=CC=CC=C1Cl ISECUHSHBOCFSW-UHFFFAOYSA-N 0.000 description 2
- WYWQGEBWXNHMOB-UHFFFAOYSA-N 4-chloro-2-n-(3-chlorophenyl)benzene-1,2-diamine Chemical compound NC1=CC=C(Cl)C=C1NC1=CC=CC(Cl)=C1 WYWQGEBWXNHMOB-UHFFFAOYSA-N 0.000 description 2
- XXFZDUZSCZDHRW-UHFFFAOYSA-N 4-chloro-2-n-(cyclohexylmethyl)benzene-1,2-diamine Chemical compound NC1=CC=C(Cl)C=C1NCC1CCCCC1 XXFZDUZSCZDHRW-UHFFFAOYSA-N 0.000 description 2
- WLQCWGCFXWCWLT-UHFFFAOYSA-N 4-chloro-2-n-cycloheptylbenzene-1,2-diamine Chemical compound NC1=CC=C(Cl)C=C1NC1CCCCCC1 WLQCWGCFXWCWLT-UHFFFAOYSA-N 0.000 description 2
- SVBZPQNRYFSPPK-UHFFFAOYSA-N 4-chloro-2-n-cyclohexylbenzene-1,2-diamine Chemical compound NC1=CC=C(Cl)C=C1NC1CCCCC1 SVBZPQNRYFSPPK-UHFFFAOYSA-N 0.000 description 2
- RTJNEARTHXXZIV-UHFFFAOYSA-N 4-ethoxy-2-n-(1-methoxy-2-methylpropan-2-yl)benzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NC(C)(C)COC)=C1 RTJNEARTHXXZIV-UHFFFAOYSA-N 0.000 description 2
- JHNLOUYGPZIFMC-UHFFFAOYSA-N 4-ethoxy-2-n-(2,4,4-trimethylpentan-2-yl)benzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NC(C)(C)CC(C)(C)C)=C1 JHNLOUYGPZIFMC-UHFFFAOYSA-N 0.000 description 2
- NXTDEAWRDAHECV-UHFFFAOYSA-N 4-ethoxy-2-n-(2-morpholin-4-ylethyl)-1-nitrocyclohexa-3,5-diene-1,2-diamine Chemical compound [O-][N+](=O)C1(N)C=CC(OCC)=CC1NCCN1CCOCC1 NXTDEAWRDAHECV-UHFFFAOYSA-N 0.000 description 2
- OIIZGXDFRVWFMR-UHFFFAOYSA-N 4-ethoxy-2-n-(4-methoxyphenyl)benzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NC=2C=CC(OC)=CC=2)=C1 OIIZGXDFRVWFMR-UHFFFAOYSA-N 0.000 description 2
- DKPHEWHTXYZJEN-UHFFFAOYSA-N 4-ethoxy-2-n-(4-methylpiperazin-1-yl)benzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NN2CCN(C)CC2)=C1 DKPHEWHTXYZJEN-UHFFFAOYSA-N 0.000 description 2
- OEZFLEULBODCEW-UHFFFAOYSA-N 4-ethoxy-2-n-(4-propan-2-ylphenyl)benzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NC=2C=CC(=CC=2)C(C)C)=C1 OEZFLEULBODCEW-UHFFFAOYSA-N 0.000 description 2
- RFOKXMAOHYQQCE-UHFFFAOYSA-N 4-ethoxy-2-n-(oxan-4-yl)benzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NC2CCOCC2)=C1 RFOKXMAOHYQQCE-UHFFFAOYSA-N 0.000 description 2
- XTTHKRHENVRJES-UHFFFAOYSA-N 4-ethoxy-2-n-morpholin-4-ylbenzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NN2CCOCC2)=C1 XTTHKRHENVRJES-UHFFFAOYSA-N 0.000 description 2
- RJWLLQWLBMJCFD-UHFFFAOYSA-N 4-methylpiperazin-1-amine Chemical compound CN1CCN(N)CC1 RJWLLQWLBMJCFD-UHFFFAOYSA-N 0.000 description 2
- GNGZZWTXFNFCMU-UHFFFAOYSA-N 4-n,4-n-dimethylcyclohexane-1,4-diamine Chemical compound CN(C)C1CCC(N)CC1 GNGZZWTXFNFCMU-UHFFFAOYSA-N 0.000 description 2
- JXRGUPLJCCDGKG-UHFFFAOYSA-N 4-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C=C1 JXRGUPLJCCDGKG-UHFFFAOYSA-N 0.000 description 2
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 2
- LUTDDOVVANJHDN-UHFFFAOYSA-N 5-chloro-2-nitro-n-(2,4,4-trimethylpentan-2-yl)aniline Chemical compound CC(C)(C)CC(C)(C)NC1=CC(Cl)=CC=C1[N+]([O-])=O LUTDDOVVANJHDN-UHFFFAOYSA-N 0.000 description 2
- OUWLSFQUIOJHJJ-UHFFFAOYSA-N 5-chloro-2-nitro-n-(4-propan-2-ylphenyl)aniline Chemical compound C1=CC(C(C)C)=CC=C1NC1=CC(Cl)=CC=C1[N+]([O-])=O OUWLSFQUIOJHJJ-UHFFFAOYSA-N 0.000 description 2
- WSBGFTHVDUYXGW-UHFFFAOYSA-N 5-chloro-n-(1-methoxy-2-methylpropan-2-yl)-2-nitroaniline Chemical compound COCC(C)(C)NC1=CC(Cl)=CC=C1[N+]([O-])=O WSBGFTHVDUYXGW-UHFFFAOYSA-N 0.000 description 2
- DMYXPHKHPSHKDN-UHFFFAOYSA-N 5-chloro-n-(2-chlorophenyl)-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NC1=CC=CC=C1Cl DMYXPHKHPSHKDN-UHFFFAOYSA-N 0.000 description 2
- LKGMCEFONLDCJO-UHFFFAOYSA-N 5-chloro-n-(2-morpholin-4-ylethyl)-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NCCN1CCOCC1 LKGMCEFONLDCJO-UHFFFAOYSA-N 0.000 description 2
- LQAPQCVZLKQVLN-UHFFFAOYSA-N 5-chloro-n-(3-chlorophenyl)-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NC1=CC=CC(Cl)=C1 LQAPQCVZLKQVLN-UHFFFAOYSA-N 0.000 description 2
- VXBBCGOXJQLHAJ-UHFFFAOYSA-N 5-chloro-n-(4-methoxyphenyl)-2-nitroaniline Chemical compound C1=CC(OC)=CC=C1NC1=CC(Cl)=CC=C1[N+]([O-])=O VXBBCGOXJQLHAJ-UHFFFAOYSA-N 0.000 description 2
- UILYFVHAUQDYMB-UHFFFAOYSA-N 5-chloro-n-(cyclohexylmethyl)-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NCC1CCCCC1 UILYFVHAUQDYMB-UHFFFAOYSA-N 0.000 description 2
- WGKAOCCZCHUWTK-UHFFFAOYSA-N 5-chloro-n-cyclopentyl-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NC1CCCC1 WGKAOCCZCHUWTK-UHFFFAOYSA-N 0.000 description 2
- JTNMTVPGVIMIII-UHFFFAOYSA-N 5-ethoxy-2-nitro-n-(2,4,4-trimethylpentan-2-yl)aniline Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NC(C)(C)CC(C)(C)C)=C1 JTNMTVPGVIMIII-UHFFFAOYSA-N 0.000 description 2
- JQYLIMWAUSLMSB-UHFFFAOYSA-N 5-ethoxy-2-nitro-n-(4-propan-2-ylphenyl)aniline Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NC=2C=CC(=CC=2)C(C)C)=C1 JQYLIMWAUSLMSB-UHFFFAOYSA-N 0.000 description 2
- HKVORKJBIYBAQR-UHFFFAOYSA-N 5-ethoxy-n-(1-methoxy-2-methylpropan-2-yl)-2-nitroaniline Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NC(C)(C)COC)=C1 HKVORKJBIYBAQR-UHFFFAOYSA-N 0.000 description 2
- ITTMJIQCMFYJSL-UHFFFAOYSA-N 5-ethoxy-n-(2-morpholin-4-ylethyl)-2-nitroaniline Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NCCN2CCOCC2)=C1 ITTMJIQCMFYJSL-UHFFFAOYSA-N 0.000 description 2
- SSWLXMMGDQGKQU-UHFFFAOYSA-N 5-ethoxy-n-(4-methoxyphenyl)-2-nitroaniline Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NC=2C=CC(OC)=CC=2)=C1 SSWLXMMGDQGKQU-UHFFFAOYSA-N 0.000 description 2
- 239000000275 Adrenocorticotropic Hormone Substances 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 101800000414 Corticotropin Proteins 0.000 description 2
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- PXXNTAGJWPJAGM-VCOUNFBDSA-N Decaline Chemical compound C=1([C@@H]2C3)C=C(OC)C(OC)=CC=1OC(C=C1)=CC=C1CCC(=O)O[C@H]3C[C@H]1N2CCCC1 PXXNTAGJWPJAGM-VCOUNFBDSA-N 0.000 description 2
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
- 208000008967 Enuresis Diseases 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 208000031220 Hemophilia Diseases 0.000 description 2
- 208000009292 Hemophilia A Diseases 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010021036 Hyponatraemia Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- BZORFPDSXLZWJF-UHFFFAOYSA-N N,N-dimethyl-1,4-phenylenediamine Chemical compound CN(C)C1=CC=C(N)C=C1 BZORFPDSXLZWJF-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 206010047163 Vasospasm Diseases 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000002686 anti-diuretic effect Effects 0.000 description 2
- 235000015278 beef Nutrition 0.000 description 2
- 238000009739 binding Methods 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 2
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 2
- 229960000258 corticotropin Drugs 0.000 description 2
- VXVVUHQULXCUPF-UHFFFAOYSA-N cycloheptanamine Chemical compound NC1CCCCCC1 VXVVUHQULXCUPF-UHFFFAOYSA-N 0.000 description 2
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 2
- SKYSRIRYMSLOIN-UHFFFAOYSA-N cyclopentolate Chemical compound C1CCCC1(O)C(C(=O)OCCN(C)C)C1=CC=CC=C1 SKYSRIRYMSLOIN-UHFFFAOYSA-N 0.000 description 2
- 229960001815 cyclopentolate Drugs 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 201000010064 diabetes insipidus Diseases 0.000 description 2
- 125000005265 dialkylamine group Chemical group 0.000 description 2
- ZZTSQZQUWBFTAT-UHFFFAOYSA-N diethylcyanamide Chemical compound CCN(CC)C#N ZZTSQZQUWBFTAT-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000001882 diuretic effect Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 201000008284 inappropriate ADH syndrome Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 210000005075 mammary gland Anatomy 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- MKQLBNJQQZRQJU-UHFFFAOYSA-N morpholin-4-amine Chemical compound NN1CCOCC1 MKQLBNJQQZRQJU-UHFFFAOYSA-N 0.000 description 2
- CURJNMSGPBXOGK-UHFFFAOYSA-N n',n'-di(propan-2-yl)ethane-1,2-diamine Chemical compound CC(C)N(C(C)C)CCN CURJNMSGPBXOGK-UHFFFAOYSA-N 0.000 description 2
- WLZNFTKVIMJMBG-UHFFFAOYSA-N n-(2-chlorophenyl)-5-ethoxy-2-nitroaniline Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NC=2C(=CC=CC=2)Cl)=C1 WLZNFTKVIMJMBG-UHFFFAOYSA-N 0.000 description 2
- ORMUIIJQBBMNPR-UHFFFAOYSA-N n-(5-chloro-2-nitrophenyl)-2,3-dihydro-1h-inden-2-amine Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NC1CC2=CC=CC=C2C1 ORMUIIJQBBMNPR-UHFFFAOYSA-N 0.000 description 2
- RYGMEXPMXCALHP-UHFFFAOYSA-N n-(5-chloro-2-nitrophenyl)-4-methylpiperazin-1-amine Chemical compound C1CN(C)CCN1NC1=CC(Cl)=CC=C1[N+]([O-])=O RYGMEXPMXCALHP-UHFFFAOYSA-N 0.000 description 2
- JNYQGXKQZICUPY-UHFFFAOYSA-N n-(5-chloro-2-nitrophenyl)adamantan-1-amine Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NC1(C2)CC(C3)CC2CC3C1 JNYQGXKQZICUPY-UHFFFAOYSA-N 0.000 description 2
- YLDQDNHAPHWBFX-UHFFFAOYSA-N n-(5-chloro-2-nitrophenyl)cycloheptanamine Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NC1CCCCCC1 YLDQDNHAPHWBFX-UHFFFAOYSA-N 0.000 description 2
- QZCXYCYVMNPFGK-UHFFFAOYSA-N n-(5-chloro-2-nitrophenyl)morpholin-4-amine Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NN1CCOCC1 QZCXYCYVMNPFGK-UHFFFAOYSA-N 0.000 description 2
- JLAOTUNEXHNRRH-UHFFFAOYSA-N n-(5-chloro-2-nitrophenyl)oxan-4-amine Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NC1CCOCC1 JLAOTUNEXHNRRH-UHFFFAOYSA-N 0.000 description 2
- OLMDKJXSHBSGNH-UHFFFAOYSA-N n-(5-ethoxy-2-nitrophenyl)-4-methylpiperazin-1-amine Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NN2CCN(C)CC2)=C1 OLMDKJXSHBSGNH-UHFFFAOYSA-N 0.000 description 2
- CYIXFIORXAHAGA-UHFFFAOYSA-N n-(5-ethoxy-2-nitrophenyl)cycloheptanamine Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NC2CCCCCC2)=C1 CYIXFIORXAHAGA-UHFFFAOYSA-N 0.000 description 2
- XOIANPFZZXMSOF-UHFFFAOYSA-N n-(5-ethoxy-2-nitrophenyl)morpholin-4-amine Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NN2CCOCC2)=C1 XOIANPFZZXMSOF-UHFFFAOYSA-N 0.000 description 2
- FEBMNTIUYFHUPE-UHFFFAOYSA-N n-(5-ethoxy-2-nitrophenyl)oxan-4-amine Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NC2CCOCC2)=C1 FEBMNTIUYFHUPE-UHFFFAOYSA-N 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- HGOGBHZZOULVKY-UHFFFAOYSA-N n-cyclohexyl-5-(2-methoxyethoxy)-2-nitroaniline Chemical compound COCCOC1=CC=C([N+]([O-])=O)C(NC2CCCCC2)=C1 HGOGBHZZOULVKY-UHFFFAOYSA-N 0.000 description 2
- XIWISJYTVRURHF-UHFFFAOYSA-N n-cyclohexyl-5-cyclopentyloxy-2-nitroaniline Chemical compound C1=C(NC2CCCCC2)C([N+](=O)[O-])=CC=C1OC1CCCC1 XIWISJYTVRURHF-UHFFFAOYSA-N 0.000 description 2
- ITMYHFRFSIFKSL-UHFFFAOYSA-N n-cyclohexyl-5-ethoxy-2-nitroaniline Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NC2CCCCC2)=C1 ITMYHFRFSIFKSL-UHFFFAOYSA-N 0.000 description 2
- POAMYENGQDEXSJ-UHFFFAOYSA-N n-cyclohexyl-5-methoxy-2-nitroaniline Chemical compound COC1=CC=C([N+]([O-])=O)C(NC2CCCCC2)=C1 POAMYENGQDEXSJ-UHFFFAOYSA-N 0.000 description 2
- KNODYQDIVHCDII-UHFFFAOYSA-N n-cyclopentyl-5-ethoxy-2-nitroaniline Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NC2CCCC2)=C1 KNODYQDIVHCDII-UHFFFAOYSA-N 0.000 description 2
- RIVIDPPYRINTTH-UHFFFAOYSA-N n-ethylpropan-2-amine Chemical compound CCNC(C)C RIVIDPPYRINTTH-UHFFFAOYSA-N 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- HKUNJDFIUVNXJG-UHFFFAOYSA-N n-tert-butyl-4-[5-ethoxy-3-(1-methoxy-2-methylpropan-2-yl)-2-oxobenzimidazol-1-yl]sulfonyl-3-methoxybenzamide Chemical compound O=C1N(C(C)(C)COC)C2=CC(OCC)=CC=C2N1S(=O)(=O)C1=CC=C(C(=O)NC(C)(C)C)C=C1OC HKUNJDFIUVNXJG-UHFFFAOYSA-N 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 2
- AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 2
- LRTFPLFDLJYEKT-UHFFFAOYSA-N para-isopropylaniline Chemical compound CC(C)C1=CC=C(N)C=C1 LRTFPLFDLJYEKT-UHFFFAOYSA-N 0.000 description 2
- 210000001428 peripheral nervous system Anatomy 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 239000011135 tin Substances 0.000 description 2
- 229910052718 tin Inorganic materials 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- SDGKUVSVPIIUCF-KNVOCYPGSA-N (2r,6s)-2,6-dimethylpiperidine Chemical compound C[C@H]1CCC[C@@H](C)N1 SDGKUVSVPIIUCF-KNVOCYPGSA-N 0.000 description 1
- CNWDJJXLPCARBH-WLHGVMLRSA-N (e)-but-2-enedioic acid;n-[4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]-2-(diethylamino)acetamide Chemical compound OC(=O)\C=C\C(O)=O.C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(NC(=O)CN(CC)CC)=CC=2)OC)C(=O)N1C1CCCCC1 CNWDJJXLPCARBH-WLHGVMLRSA-N 0.000 description 1
- KGKAYWMGPDWLQZ-UHFFFAOYSA-N 1,2-bis(bromomethyl)benzene Chemical group BrCC1=CC=CC=C1CBr KGKAYWMGPDWLQZ-UHFFFAOYSA-N 0.000 description 1
- SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical compound C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 description 1
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- KZZCMXMAJLXRSW-UHFFFAOYSA-N 1-(2,4-dimethoxyphenyl)sulfonyl-3-[2-[di(propan-2-yl)amino]ethyl]-5-ethoxybenzimidazol-2-one Chemical compound O=C1N(CCN(C(C)C)C(C)C)C2=CC(OCC)=CC=C2N1S(=O)(=O)C1=CC=C(OC)C=C1OC KZZCMXMAJLXRSW-UHFFFAOYSA-N 0.000 description 1
- HALGNMKAERYSPW-UHFFFAOYSA-N 1-(2,4-dimethoxyphenyl)sulfonyl-5-ethoxy-3-(2-morpholin-4-ylethyl)benzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(OC)=CC=2)OC)C(=O)N1CCN1CCOCC1 HALGNMKAERYSPW-UHFFFAOYSA-N 0.000 description 1
- GTLLEORMOWFJHS-UHFFFAOYSA-N 1-(4-amino-2-methoxyphenyl)sulfonyl-5-chloro-3-cycloheptylbenzimidazol-2-one Chemical compound COC1=CC(N)=CC=C1S(=O)(=O)N1C(=O)N(C2CCCCCC2)C2=CC(Cl)=CC=C21 GTLLEORMOWFJHS-UHFFFAOYSA-N 0.000 description 1
- BUGUKDBWOJCXPW-UHFFFAOYSA-N 1-(4-amino-2-methoxyphenyl)sulfonyl-5-chloro-3-cyclohexylbenzimidazol-2-one Chemical compound COC1=CC(N)=CC=C1S(=O)(=O)N1C(=O)N(C2CCCCC2)C2=CC(Cl)=CC=C21 BUGUKDBWOJCXPW-UHFFFAOYSA-N 0.000 description 1
- JNLFPXJEFQFUGS-UHFFFAOYSA-N 1-(4-amino-2-methoxyphenyl)sulfonyl-5-chloro-3-phenylbenzimidazol-2-one Chemical compound COC1=CC(N)=CC=C1S(=O)(=O)N1C(=O)N(C=2C=CC=CC=2)C2=CC(Cl)=CC=C21 JNLFPXJEFQFUGS-UHFFFAOYSA-N 0.000 description 1
- DPMHUPPKNWDHKN-UHFFFAOYSA-N 1-(4-amino-2-methoxyphenyl)sulfonyl-5-ethoxy-3-(2,4,4-trimethylpentan-2-yl)benzimidazol-2-one Chemical compound O=C1N(C(C)(C)CC(C)(C)C)C2=CC(OCC)=CC=C2N1S(=O)(=O)C1=CC=C(N)C=C1OC DPMHUPPKNWDHKN-UHFFFAOYSA-N 0.000 description 1
- QDUKKYZKWBDAFN-UHFFFAOYSA-N 1-(4-amino-2-methoxyphenyl)sulfonyl-5-ethoxy-3-pyridin-2-ylbenzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(N)=CC=2)OC)C(=O)N1C1=CC=CC=N1 QDUKKYZKWBDAFN-UHFFFAOYSA-N 0.000 description 1
- HCXJGDUJTWOLFY-UHFFFAOYSA-N 1-tert-butyl-3-[4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]-1-methylurea Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(NC(=O)N(C)C(C)(C)C)=CC=2)OC)C(=O)N1C1CCCCC1 HCXJGDUJTWOLFY-UHFFFAOYSA-N 0.000 description 1
- IOPYKQIHIVEQCB-UHFFFAOYSA-N 1-tert-butyl-3-[4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]urea Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(NC(=O)NC(C)(C)C)=CC=2)OC)C(=O)N1C1CCCCC1 IOPYKQIHIVEQCB-UHFFFAOYSA-N 0.000 description 1
- XZCODEYRFXUYGC-UHFFFAOYSA-N 2-(1-adamantyl)-4-ethoxybenzene-1,3-diamine Chemical compound C12(CC3CC(CC(C1)C3)C2)C1=C(C=CC(=C1N)OCC)N XZCODEYRFXUYGC-UHFFFAOYSA-N 0.000 description 1
- IMMOTHAWSMMOOV-UHFFFAOYSA-N 2-(1-adamantyl)-6-ethoxy-3-nitroaniline Chemical compound C12(CC3CC(CC(C1)C3)C2)C1=C(C=CC(=C1N)OCC)[N+](=O)[O-] IMMOTHAWSMMOOV-UHFFFAOYSA-N 0.000 description 1
- WZMNQQVAVZAEHV-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-yl)-4-ethoxybenzene-1,3-diamine Chemical compound NC1=C(C(=C(C=C1)OCC)N)C1CC2=CC=CC=C2C1 WZMNQQVAVZAEHV-UHFFFAOYSA-N 0.000 description 1
- DFFCOKIUKXWVBG-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-yl)-6-ethoxy-3-nitroaniline Chemical compound C(C)OC1=C(C(=C(C=C1)[N+](=O)[O-])C1CC2=CC=CC=C2C1)N DFFCOKIUKXWVBG-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- LMHHFZAXSANGGM-UHFFFAOYSA-N 2-aminoindane Chemical compound C1=CC=C2CC(N)CC2=C1 LMHHFZAXSANGGM-UHFFFAOYSA-N 0.000 description 1
- LGSXZCWAQOLAMX-UHFFFAOYSA-N 2-chloro-n-[4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]acetamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(NC(=O)CCl)=CC=2)OC)C(=O)N1C1CCCCC1 LGSXZCWAQOLAMX-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- SMUKODJVMQOSAB-UHFFFAOYSA-N 2-ethylbutanoyl chloride Chemical compound CCC(CC)C(Cl)=O SMUKODJVMQOSAB-UHFFFAOYSA-N 0.000 description 1
- TXFUTUXTGJVIJE-UHFFFAOYSA-N 2-n-(1-adamantyl)-4-ethoxybenzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NC23CC4CC(CC(C4)C2)C3)=C1 TXFUTUXTGJVIJE-UHFFFAOYSA-N 0.000 description 1
- FFVDOVQGXYLKIR-UHFFFAOYSA-N 2-n-(2,3-dihydro-1h-inden-2-yl)-4-ethoxybenzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NC2CC3=CC=CC=C3C2)=C1 FFVDOVQGXYLKIR-UHFFFAOYSA-N 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- GUGQQGROXHPINL-UHFFFAOYSA-N 2-oxobutanoyl chloride Chemical compound CCC(=O)C(Cl)=O GUGQQGROXHPINL-UHFFFAOYSA-N 0.000 description 1
- RSJSYCZYQNJQPY-UHFFFAOYSA-N 3,4-dimethoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1OC RSJSYCZYQNJQPY-UHFFFAOYSA-N 0.000 description 1
- AOPUKUZMBXFPDI-UHFFFAOYSA-N 3-(1-adamantyl)-1-(4-amino-2-methoxyphenyl)sulfonyl-5-ethoxybenzimidazol-2-one Chemical compound O=C1N(C23CC4CC(CC(C4)C2)C3)C2=CC(OCC)=CC=C2N1S(=O)(=O)C1=CC=C(N)C=C1OC AOPUKUZMBXFPDI-UHFFFAOYSA-N 0.000 description 1
- IMWPICOFQNCCET-UHFFFAOYSA-N 3-(1-adamantyl)-5-ethoxy-1-(2-methoxy-4-nitrophenyl)sulfonylbenzimidazol-2-one Chemical compound O=C1N(C23CC4CC(CC(C4)C2)C3)C2=CC(OCC)=CC=C2N1S(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1OC IMWPICOFQNCCET-UHFFFAOYSA-N 0.000 description 1
- RAGSIFSXIUVKRV-UHFFFAOYSA-M 3-(1-benzyl-1-methylpiperidin-1-ium-4-yl)-5-chloro-1-(2,4-dimethoxyphenyl)sulfonylbenzimidazol-2-one;iodide Chemical compound [I-].COC1=CC(OC)=CC=C1S(=O)(=O)N1C(=O)N(C2CC[N+](C)(CC=3C=CC=CC=3)CC2)C2=CC(Cl)=CC=C21 RAGSIFSXIUVKRV-UHFFFAOYSA-M 0.000 description 1
- YIUCYIPGEXSVKN-UHFFFAOYSA-N 3-[4-[5-chloro-3-(2-chlorophenyl)-2-oxobenzimidazol-1-yl]sulfonylphenyl]-1,1-diethylurea Chemical compound C1=CC(NC(=O)N(CC)CC)=CC=C1S(=O)(=O)N1C(=O)N(C=2C(=CC=CC=2)Cl)C2=CC(Cl)=CC=C21 YIUCYIPGEXSVKN-UHFFFAOYSA-N 0.000 description 1
- NXSIMGDQRVGAQJ-UHFFFAOYSA-N 3-[4-[5-ethoxy-2-oxo-3-(2,4,4-trimethylpentan-2-yl)benzimidazol-1-yl]sulfonyl-3-methoxyphenyl]-1,1-diethylurea Chemical compound O=C1N(C(C)(C)CC(C)(C)C)C2=CC(OCC)=CC=C2N1S(=O)(=O)C1=CC=C(NC(=O)N(CC)CC)C=C1OC NXSIMGDQRVGAQJ-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 1
- FDGYCGZJAZSLKX-UHFFFAOYSA-N 3-cyclohexyl-5-ethoxy-1-(2-methoxy-4-nitrophenyl)sulfonylbenzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)[N+]([O-])=O)OC)C(=O)N1C1CCCCC1 FDGYCGZJAZSLKX-UHFFFAOYSA-N 0.000 description 1
- IJBCECVRPCTIMX-UHFFFAOYSA-N 3-cyclohexyl-5-methoxy-1-(4-nitrophenyl)sulfonylbenzimidazol-2-one Chemical compound C12=CC(OC)=CC=C2N(S(=O)(=O)C=2C=CC(=CC=2)[N+]([O-])=O)C(=O)N1C1CCCCC1 IJBCECVRPCTIMX-UHFFFAOYSA-N 0.000 description 1
- SDKJJAKGOABBBD-UHFFFAOYSA-N 4,6-dimethoxybenzene-1,3-disulfonyl chloride Chemical compound COC1=CC(OC)=C(S(Cl)(=O)=O)C=C1S(Cl)(=O)=O SDKJJAKGOABBBD-UHFFFAOYSA-N 0.000 description 1
- TZZNAAQEMIKQIL-UHFFFAOYSA-N 4-(3-cycloheptyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxybenzoic acid Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(O)=O)OC)C(=O)N1C1CCCCCC1 TZZNAAQEMIKQIL-UHFFFAOYSA-N 0.000 description 1
- NUULTIAOGUWNQG-UHFFFAOYSA-N 4-(3-cyclohexyl-5-cyclopentyloxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1S(=O)(=O)N1C(=O)N(C2CCCCC2)C2=CC(OC3CCCC3)=CC=C21 NUULTIAOGUWNQG-UHFFFAOYSA-N 0.000 description 1
- WYEPCVIHYGQKLI-UHFFFAOYSA-N 4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxy-n-(1,3-thiazol-2-yl)benzamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)NC=2SC=CN=2)OC)C(=O)N1C1CCCCC1 WYEPCVIHYGQKLI-UHFFFAOYSA-N 0.000 description 1
- NUQPDERFDLWSRR-UHFFFAOYSA-N 4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxy-n-(2,4,4-trimethylpentan-2-yl)benzamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)NC(C)(C)CC(C)(C)C)OC)C(=O)N1C1CCCCC1 NUQPDERFDLWSRR-UHFFFAOYSA-N 0.000 description 1
- NJZHMOSTVRVGHK-UHFFFAOYSA-N 4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxy-n-(2-methylbutan-2-yl)benzamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)NC(C)(C)CC)OC)C(=O)N1C1CCCCC1 NJZHMOSTVRVGHK-UHFFFAOYSA-N 0.000 description 1
- UDNHXSMHANAIBE-UHFFFAOYSA-N 4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxy-n-(2-methylphenyl)benzamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)NC=2C(=CC=CC=2)C)OC)C(=O)N1C1CCCCC1 UDNHXSMHANAIBE-UHFFFAOYSA-N 0.000 description 1
- AZVTVWHDYHDYBR-UHFFFAOYSA-N 4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxybenzoic acid Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(O)=O)OC)C(=O)N1C1CCCCC1 AZVTVWHDYHDYBR-UHFFFAOYSA-N 0.000 description 1
- QIXJZWHUJBSMNY-UHFFFAOYSA-N 4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-n-(1-hydroxy-2-methylpropan-2-yl)-3-methoxybenzamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)NC(C)(C)CO)OC)C(=O)N1C1CCCCC1 QIXJZWHUJBSMNY-UHFFFAOYSA-N 0.000 description 1
- JPFPPEDULGEGQY-UHFFFAOYSA-N 4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-n-(2,3-dihydro-1h-inden-2-yl)-3-methoxybenzamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)NC2CC3=CC=CC=C3C2)OC)C(=O)N1C1CCCCC1 JPFPPEDULGEGQY-UHFFFAOYSA-N 0.000 description 1
- BXHBDLDPGQXJBN-UHFFFAOYSA-N 4-(5-ethoxy-2-oxo-3-pyridin-2-ylbenzimidazol-1-yl)sulfonyl-3-methoxy-n,n-dimethylbenzamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)N(C)C)OC)C(=O)N1C1=CC=CC=N1 BXHBDLDPGQXJBN-UHFFFAOYSA-N 0.000 description 1
- RLIMBLHEKHFIGP-UHFFFAOYSA-N 4-(diethylcarbamoylamino)benzenesulfonyl chloride Chemical compound CCN(CC)C(=O)NC1=CC=C(S(Cl)(=O)=O)C=C1 RLIMBLHEKHFIGP-UHFFFAOYSA-N 0.000 description 1
- RTQAIFXZCMVBDT-UHFFFAOYSA-N 4-(dimethylamino)benzenesulfonyl chloride Chemical compound CN(C)C1=CC=C(S(Cl)(=O)=O)C=C1 RTQAIFXZCMVBDT-UHFFFAOYSA-N 0.000 description 1
- YSYQMEJYSSIBLC-UHFFFAOYSA-N 4-[3-cyclohexyl-5-(2-methoxyethoxy)-2-oxobenzimidazol-1-yl]sulfonyl-3-methoxybenzoic acid Chemical compound C12=CC(OCCOC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(O)=O)OC)C(=O)N1C1CCCCC1 YSYQMEJYSSIBLC-UHFFFAOYSA-N 0.000 description 1
- QGWQXURUOLYXMI-UHFFFAOYSA-N 4-[5-ethoxy-3-(1-methoxy-2-methylpropan-2-yl)-2-oxobenzimidazol-1-yl]sulfonyl-3-methoxybenzoic acid Chemical compound O=C1N(C(C)(C)COC)C2=CC(OCC)=CC=C2N1S(=O)(=O)C1=CC=C(C(O)=O)C=C1OC QGWQXURUOLYXMI-UHFFFAOYSA-N 0.000 description 1
- PQZHBBXFNLYMCQ-UHFFFAOYSA-N 4-[5-ethoxy-3-(oxan-4-yl)-2-oxobenzimidazol-1-yl]sulfonyl-3-methoxybenzoic acid Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(O)=O)OC)C(=O)N1C1CCOCC1 PQZHBBXFNLYMCQ-UHFFFAOYSA-N 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- CDIIZULDSLKBKV-UHFFFAOYSA-N 4-chlorobutanoyl chloride Chemical compound ClCCCC(Cl)=O CDIIZULDSLKBKV-UHFFFAOYSA-N 0.000 description 1
- MYKSEYBFCBPGOA-UHFFFAOYSA-N 4-ethoxy-2-n-pyridin-2-ylbenzene-1,2-diamine Chemical compound CCOC1=CC=C(N)C(NC=2N=CC=CC=2)=C1 MYKSEYBFCBPGOA-UHFFFAOYSA-N 0.000 description 1
- KOLSEIFNVPJIAS-UHFFFAOYSA-N 4-ethoxy-2-pyridin-2-ylbenzene-1,3-diamine Chemical compound NC1=C(C(=C(C=C1)OCC)N)C1=NC=CC=C1 KOLSEIFNVPJIAS-UHFFFAOYSA-N 0.000 description 1
- FPJABYRHGJABIZ-UHFFFAOYSA-N 4-morpholin-4-ylbenzenesulfonyl chloride Chemical compound C1=CC(S(=O)(=O)Cl)=CC=C1N1CCOCC1 FPJABYRHGJABIZ-UHFFFAOYSA-N 0.000 description 1
- BRTDEKQMIKCPKH-UHFFFAOYSA-N 4-phenylmethoxybenzenesulfonyl chloride Chemical compound C1=CC(S(=O)(=O)Cl)=CC=C1OCC1=CC=CC=C1 BRTDEKQMIKCPKH-UHFFFAOYSA-N 0.000 description 1
- RNZLMUGMPROIEF-UHFFFAOYSA-N 5-chloro-1-(2-methoxy-4-nitrophenyl)sulfonyl-3-phenylbenzimidazol-2-one Chemical compound COC1=CC([N+]([O-])=O)=CC=C1S(=O)(=O)N1C(=O)N(C=2C=CC=CC=2)C2=CC(Cl)=CC=C21 RNZLMUGMPROIEF-UHFFFAOYSA-N 0.000 description 1
- WPCAJOICRFAZGH-UHFFFAOYSA-N 5-chloro-1-(3,4-dimethoxyphenyl)sulfonyl-3-phenylbenzimidazol-2-one Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)N1C(=O)N(C=2C=CC=CC=2)C2=CC(Cl)=CC=C21 WPCAJOICRFAZGH-UHFFFAOYSA-N 0.000 description 1
- BYZWBVYZTNUFGO-UHFFFAOYSA-N 5-chloro-3-cycloheptyl-1-(2-methoxy-4-nitrophenyl)sulfonylbenzimidazol-2-one Chemical compound COC1=CC([N+]([O-])=O)=CC=C1S(=O)(=O)N1C(=O)N(C2CCCCCC2)C2=CC(Cl)=CC=C21 BYZWBVYZTNUFGO-UHFFFAOYSA-N 0.000 description 1
- LPMGLBYVTXEYMZ-UHFFFAOYSA-N 5-chloro-3-cyclohexyl-1-(4-nitrophenyl)sulfonylbenzimidazol-2-one Chemical compound C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)N1C(=O)N(C2CCCCC2)C2=CC(Cl)=CC=C21 LPMGLBYVTXEYMZ-UHFFFAOYSA-N 0.000 description 1
- ZYXNEYFVFVVUAG-UHFFFAOYSA-N 5-ethoxy-1-(2-methoxy-4-nitrophenyl)sulfonyl-3-(2,4,4-trimethylpentan-2-yl)benzimidazol-2-one Chemical compound O=C1N(C(C)(C)CC(C)(C)C)C2=CC(OCC)=CC=C2N1S(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1OC ZYXNEYFVFVVUAG-UHFFFAOYSA-N 0.000 description 1
- WWXUZHCZYWNCRK-UHFFFAOYSA-N 5-ethoxy-1-(2-methoxy-4-nitrophenyl)sulfonyl-3-pyridin-2-ylbenzimidazol-2-one Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)[N+]([O-])=O)OC)C(=O)N1C1=CC=CC=N1 WWXUZHCZYWNCRK-UHFFFAOYSA-N 0.000 description 1
- ULKQXOCUQGYGEO-UHFFFAOYSA-N 6-chloro-3-nitro-2-pyridin-2-ylaniline Chemical compound ClC1=C(C(=C(C=C1)[N+](=O)[O-])C1=NC=CC=C1)N ULKQXOCUQGYGEO-UHFFFAOYSA-N 0.000 description 1
- GTVDRSJKIFJYIF-UHFFFAOYSA-N 6-ethoxy-3-nitro-2-pyridin-2-ylaniline Chemical compound C(C)OC1=C(C(=C(C=C1)[N+](=O)[O-])C1=NC=CC=C1)N GTVDRSJKIFJYIF-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 229940123413 Angiotensin II antagonist Drugs 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003225 Arteriospasm coronary Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 208000003890 Coronary Vasospasm Diseases 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 208000005171 Dysmenorrhea Diseases 0.000 description 1
- 206010013935 Dysmenorrhoea Diseases 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 208000019025 Hypokalemia Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 206010053198 Inappropriate antidiuretic hormone secretion Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 description 1
- XTUVJUMINZSXGF-UHFFFAOYSA-N N-methylcyclohexylamine Chemical compound CNC1CCCCC1 XTUVJUMINZSXGF-UHFFFAOYSA-N 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 208000006399 Premature Obstetric Labor Diseases 0.000 description 1
- 206010036600 Premature labour Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 208000003782 Raynaud disease Diseases 0.000 description 1
- 208000012322 Raynaud phenomenon Diseases 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 229940083335 Vasopressin agonist Drugs 0.000 description 1
- 229940116211 Vasopressin antagonist Drugs 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- QWQONZVLXJGXHV-UHFFFAOYSA-N [chlorosulfonyloxy(dimethyl)silyl]methane Chemical compound C[Si](C)(C)OS(Cl)(=O)=O QWQONZVLXJGXHV-UHFFFAOYSA-N 0.000 description 1
- 238000012084 abdominal surgery Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 239000000951 adrenergic alpha-1 receptor antagonist Substances 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- WOLHOYHSEKDWQH-UHFFFAOYSA-N amantadine hydrochloride Chemical compound [Cl-].C1C(C2)CC3CC2CC1([NH3+])C3 WOLHOYHSEKDWQH-UHFFFAOYSA-N 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003160 antidiuretic agent Substances 0.000 description 1
- 229940124538 antidiuretic agent Drugs 0.000 description 1
- 239000000729 antidote Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical class ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
- SWUDXVQBNMJVNS-UHFFFAOYSA-N benzyl 4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxybenzoate Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)OCC=2C=CC=CC=2)OC)C(=O)N1C1CCCCC1 SWUDXVQBNMJVNS-UHFFFAOYSA-N 0.000 description 1
- HJWLFLFHBPQTOI-UHFFFAOYSA-N benzyl 4-chlorosulfonyl-3-methoxybenzoate Chemical compound C1=C(S(Cl)(=O)=O)C(OC)=CC(C(=O)OCC=2C=CC=CC=2)=C1 HJWLFLFHBPQTOI-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- IULFXBLVJIPESI-UHFFFAOYSA-N bis(methylsulfanyl)methylidenecyanamide Chemical compound CSC(SC)=NC#N IULFXBLVJIPESI-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- NBYQXBYMEUOBON-UHFFFAOYSA-N carbamothioyl chloride Chemical compound NC(Cl)=S NBYQXBYMEUOBON-UHFFFAOYSA-N 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 201000011634 coronary artery vasospasm Diseases 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- 150000003946 cyclohexylamines Chemical class 0.000 description 1
- AVKNGPAMCBSNSO-UHFFFAOYSA-N cyclohexylmethanamine Chemical compound NCC1CCCCC1 AVKNGPAMCBSNSO-UHFFFAOYSA-N 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940082150 encore Drugs 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- GXSDQKGSOFMCFJ-UHFFFAOYSA-N ethyl 2-[[4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxybenzoyl]amino]-2-methylpropanoate Chemical compound COC1=CC(C(=O)NC(C)(C)C(=O)OCC)=CC=C1S(=O)(=O)N1C(=O)N(C2CCCCC2)C2=CC(OCC)=CC=C21 GXSDQKGSOFMCFJ-UHFFFAOYSA-N 0.000 description 1
- YREPHXXOTHNLEV-UHFFFAOYSA-N ethyl 2-amino-2-methylpropanoate;hydrochloride Chemical compound Cl.CCOC(=O)C(C)(C)N YREPHXXOTHNLEV-UHFFFAOYSA-N 0.000 description 1
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- SAVROPQJUYSBDD-UHFFFAOYSA-N formyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CO SAVROPQJUYSBDD-UHFFFAOYSA-N 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- VANNPISTIUFMLH-UHFFFAOYSA-N glutaric anhydride Chemical compound O=C1CCCC(=O)O1 VANNPISTIUFMLH-UHFFFAOYSA-N 0.000 description 1
- 125000004997 halocarbonyl group Chemical group 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 208000001286 intracranial vasospasm Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- RHMQNXNXUZLEIY-UHFFFAOYSA-N methanol;2-propan-2-yloxypropane Chemical compound OC.CC(C)OC(C)C RHMQNXNXUZLEIY-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
- RZZFNZNJGSUYOG-UHFFFAOYSA-N methyl 4-(3-cycloheptyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxybenzoate Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)OC)OC)C(=O)N1C1CCCCCC1 RZZFNZNJGSUYOG-UHFFFAOYSA-N 0.000 description 1
- OVZLSYXMPIOOJH-UHFFFAOYSA-N methyl 4-(5-ethoxy-2-oxo-3-pyridin-2-ylbenzimidazol-1-yl)sulfonyl-3-methoxybenzoate Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)OC)OC)C(=O)N1C1=CC=CC=N1 OVZLSYXMPIOOJH-UHFFFAOYSA-N 0.000 description 1
- MRYZBIZFUIAXDI-UHFFFAOYSA-N methyl 4-[3-cyclohexyl-5-(2-methoxyethoxy)-2-oxobenzimidazol-1-yl]sulfonyl-3-methoxybenzoate Chemical compound C12=CC(OCCOC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)OC)OC)C(=O)N1C1CCCCC1 MRYZBIZFUIAXDI-UHFFFAOYSA-N 0.000 description 1
- SXBHKMDEBLDGPD-UHFFFAOYSA-N methyl 4-[5-ethoxy-3-(oxan-4-yl)-2-oxobenzimidazol-1-yl]sulfonyl-3-methoxybenzoate Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)OC)OC)C(=O)N1C1CCOCC1 SXBHKMDEBLDGPD-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 201000003152 motion sickness Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- ZQGJEUVBUVKZKS-UHFFFAOYSA-N n,2-dimethylpropan-2-amine Chemical compound CNC(C)(C)C ZQGJEUVBUVKZKS-UHFFFAOYSA-N 0.000 description 1
- OFCCYDUUBNUJIB-UHFFFAOYSA-N n,n-diethylcarbamoyl chloride Chemical compound CCN(CC)C(Cl)=O OFCCYDUUBNUJIB-UHFFFAOYSA-N 0.000 description 1
- CHYOMIGAACGCKY-UHFFFAOYSA-N n-(1-adamantyl)-4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxybenzamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)NC23CC4CC(CC(C4)C2)C3)OC)C(=O)N1C1CCCCC1 CHYOMIGAACGCKY-UHFFFAOYSA-N 0.000 description 1
- VWWKIFAYGCXCFH-UHFFFAOYSA-N n-(5-chloro-2-nitrophenyl)pyridin-2-amine Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1NC1=CC=CC=N1 VWWKIFAYGCXCFH-UHFFFAOYSA-N 0.000 description 1
- YYVOUBMKNFEXON-UHFFFAOYSA-N n-(5-ethoxy-2-nitrophenyl)-2,3-dihydro-1h-inden-2-amine Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NC2CC3=CC=CC=C3C2)=C1 YYVOUBMKNFEXON-UHFFFAOYSA-N 0.000 description 1
- DQVWDYBJWHOJSR-UHFFFAOYSA-N n-(5-ethoxy-2-nitrophenyl)adamantan-1-amine Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NC23CC4CC(CC(C4)C2)C3)=C1 DQVWDYBJWHOJSR-UHFFFAOYSA-N 0.000 description 1
- CNDMNOVHDXYOKG-UHFFFAOYSA-N n-(5-ethoxy-2-nitrophenyl)pyridin-2-amine Chemical compound CCOC1=CC=C([N+]([O-])=O)C(NC=2N=CC=CC=2)=C1 CNDMNOVHDXYOKG-UHFFFAOYSA-N 0.000 description 1
- COGGGWRHZQTITF-UHFFFAOYSA-N n-(oxan-4-ylidene)hydroxylamine Chemical compound ON=C1CCOCC1 COGGGWRHZQTITF-UHFFFAOYSA-N 0.000 description 1
- AGOSQXNASHHAOS-UHFFFAOYSA-N n-[4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]-2-ethylbutanamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(NC(=O)C(CC)CC)=CC=2)OC)C(=O)N1C1CCCCC1 AGOSQXNASHHAOS-UHFFFAOYSA-N 0.000 description 1
- QRVXUFNBVCOQSX-UHFFFAOYSA-N n-[4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]-2-methylbenzamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(NC(=O)C=3C(=CC=CC=3)C)=CC=2)OC)C(=O)N1C1CCCCC1 QRVXUFNBVCOQSX-UHFFFAOYSA-N 0.000 description 1
- LDSDPZNXJCNDKG-UHFFFAOYSA-N n-[4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]piperidine-1-carboxamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(NC(=O)N3CCCCC3)=CC=2)OC)C(=O)N1C1CCCCC1 LDSDPZNXJCNDKG-UHFFFAOYSA-N 0.000 description 1
- NPPQFGPJBDSUAG-UHFFFAOYSA-N n-tert-butyl-4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxybenzamide Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(=CC=2)C(=O)NC(C)(C)C)OC)C(=O)N1C1CCCCC1 NPPQFGPJBDSUAG-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 150000005440 nitrobenzoic acid derivatives Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000009935 nitrosation Effects 0.000 description 1
- 238000007034 nitrosation reaction Methods 0.000 description 1
- KOSYAAIZOGNATQ-UHFFFAOYSA-N o-phenyl chloromethanethioate Chemical compound ClC(=S)OC1=CC=CC=C1 KOSYAAIZOGNATQ-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000032696 parturition Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- 239000000810 peripheral vasodilating agent Substances 0.000 description 1
- 229960002116 peripheral vasodilator Drugs 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- FKZZDBVTIOPHBX-UHFFFAOYSA-N phenyl n-[4-(3-cyclohexyl-5-ethoxy-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]carbamate Chemical compound C12=CC(OCC)=CC=C2N(S(=O)(=O)C=2C(=CC(NC(=O)OC=3C=CC=CC=3)=CC=2)OC)C(=O)N1C1CCCCC1 FKZZDBVTIOPHBX-UHFFFAOYSA-N 0.000 description 1
- XDHFXQZMRUMSTA-UHFFFAOYSA-N phenyl n-[4-(5-chloro-3-cycloheptyl-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]carbamate Chemical compound C=1C=C(S(=O)(=O)N2C(N(C3CCCCCC3)C3=CC(Cl)=CC=C32)=O)C(OC)=CC=1NC(=O)OC1=CC=CC=C1 XDHFXQZMRUMSTA-UHFFFAOYSA-N 0.000 description 1
- YIUOXKLSQBZQGR-UHFFFAOYSA-N phenyl n-[4-(5-chloro-3-cyclohexyl-2-oxobenzimidazol-1-yl)sulfonyl-3-methoxyphenyl]carbamate Chemical compound C=1C=C(S(=O)(=O)N2C(N(C3CCCCC3)C3=CC(Cl)=CC=C32)=O)C(OC)=CC=1NC(=O)OC1=CC=CC=C1 YIUOXKLSQBZQGR-UHFFFAOYSA-N 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 208000024896 potassium deficiency disease Diseases 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 208000026440 premature labor Diseases 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 230000009076 regulation of hemostasis Effects 0.000 description 1
- 210000005227 renal system Anatomy 0.000 description 1
- 239000002461 renin inhibitor Substances 0.000 description 1
- 230000036454 renin-angiotensin system Effects 0.000 description 1
- 229940086526 renin-inhibitors Drugs 0.000 description 1
- 102220113114 rs7248372 Human genes 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- BLXAGSNYHSQSRC-UHFFFAOYSA-M sodium;2-hydroxybenzenesulfonate Chemical compound [Na+].OC1=CC=CC=C1S([O-])(=O)=O BLXAGSNYHSQSRC-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001300 stimulation of adenylate cyclase Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 239000003038 vasopressin antagonist Substances 0.000 description 1
- 239000002536 vasopressin receptor antagonist Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 108010047303 von Willebrand Factor Proteins 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/22—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms directly attached to ring nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/26—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Definitions
- the subject of the present invention is derivatives of 1-benzenesulfonyl-1,3-dihydro-2 H -benzimidazol-2-one, their preparation and the pharmaceutical compositions containing them.
- the 1-benzenesulfonyl-1,3-dihydro-2 H -benzimidazol-2-one derivatives according to the present invention have an affinity for the vasopressin and oxytocin receptors.
- Vasopressin is a hormone known for its antidiuretic effect and its effect in the regulation of blood pressure. It stimulates several types of receptors: V1 (V 1a , V 1b ), V2. These receptors are located in the liver, vessels (coronary, renal, cerebral), platelets, kidney, uterus, adrenal glands, central nervous system, pituitary gland. Oxytocin has a peptide structure close to that of vasopressin. Oxytocin receptors are also found on the smooth muscle of the uterus, they are also found on myoepithelial cells of the mammary gland, in the central nervous system and in the kidney. The location of the different receptors is described in: S.
- Vasopressin thus exerts cardiovascular, hepatic, antidiuretic, aggregating effects and effects on the central and peripheral nervous system, and on the uterine sphere. Oxytocin is involved in parturition, lactation and sexual behavior.
- Vasopressin receptor antagonists can act on the regulation of central and peripheral circulation, in particular coronary, renal and gastric circulation, as well as on water regulation and the release of adrenocorticotrophic hormone (ACTH).
- Vasopressin agonists can advantageously replace vasopressin or its analogues in the treatment of diabetes insipidus; they can also be used in the treatment of enuresis, and in the regulation of hemostasis: treatment of hemophilia, Von syndrome Willebrand, antidote for platelet aggregators, FA LASZLO ,, Pharmacol.
- vasopressin and oxytocin as well as some of their peptide or non-peptide analogues are used in therapy and have shown their effectiveness.
- Vasopressin P. GROSS et al. ed. John Libbey Eurotext, 1993, in particular 243-257 and 549-562.
- FA LASZLO and FA LASZLO Jr. Clinical perspectives for vasopressin antagonists, Drug News Perspect., 1993, 6 (8); WG NORTH, J. Clin.
- the compounds according to the invention are useful in particular in the treatment of affections of the central and peripheral nervous system, of the cardiovascular system, of the renal sphere, of the gastric sphere and in disorders of sexual behavior, in men and in men. 'animal.
- the invention includes all the optical isomers of this compound.
- the salts of the compounds of formula (I) according to the present invention include those with mineral or organic acids which allow suitable separation or crystallization of the compounds of formula (I), such as picric acid, oxalic acid or a optically active acid, for example a mandelic acid or a camphosulfonic acid, and those which form physiologically acceptable salts such as the hydrochloride, the hydrobromide, the sulfate, the hydrogen sulfate, the dihydrogen phosphate, the maleate, the fumarate, the 2-naphthalenesulfonate .
- mineral or organic acids which allow suitable separation or crystallization of the compounds of formula (I)
- picric acid such as picric acid, oxalic acid or a optically active acid, for example a mandelic acid or a camphosulfonic acid
- physiologically acceptable salts such as the hydrochloride, the hydrobromide, the sulfate, the hydrogen sulfate, the dihydrogen phosphate,
- the salts of the compounds of formula (I) also include the salts with organic or inorganic bases, for example the alkali or alkaline earth metal salts such as the sodium, potassium, calcium salts, the sodium and potassium being preferred, or with an amine, such as trometamol, or else the salts of arginine, of lysine, or of any physiologically acceptable amine.
- organic or inorganic bases for example the alkali or alkaline earth metal salts such as the sodium, potassium, calcium salts, the sodium and potassium being preferred, or with an amine, such as trometamol, or else the salts of arginine, of lysine, or of any physiologically acceptable amine.
- halogen means an atom chosen from fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine.
- the nitrogen protecting group means a group such as: a (C1-C7) alkyl, for example methyl or tert- butyl; benzyl; substituted benzyl such as p-nitrobenzyl, p-chlorobenzyl, p-methoxybenzyl; benzhydryl; a trityl; benzoyl; a (C1-C4) alkylcarbonyl, for example acetyl; a (C1-C4) alkoxycarbonyl, for example a methoxycarbonyl, an ethoxycarbonyl or a tert -butoxycarbonyl; a benzyloxycarbonyl.
- a (C1-C7) alkyl for example methyl or tert- butyl
- benzyl substituted benzyl such as p-nitrobenzyl, p-chlorobenzyl, p-methoxybenzyl
- benzhydryl a
- C1-C7 or C1-C8 or C1-C4 alkyl is understood to mean a straight or branched C1-C7 or C en-C8 or C1-C4 alkyl.
- C1-C7 or C1-C4 alkoxy is meant a straight or branched C1-C7 or respectively C1-C4 alkoxy.
- step 1 is carried out in an anhydrous solvent such as DMF or THF, in the presence of a metal hydride such as sodium hydride for example, or in the presence of an alcoholate such as tert-butoxide potassium.
- an anhydrous solvent such as DMF or THF
- a metal hydride such as sodium hydride for example
- an alcoholate such as tert-butoxide potassium
- Benzimidazol-2-ones (II) derivatives are known or can be prepared according to different procedures by known methods.
- N-substituted benzimidazol-2-ones (II), useful as starting materials for the preparation of the compounds according to the invention can be prepared, according to methods described in patents GB 2 127 408, GB 1 575 386; patent applications JP 62-249 982, JP 53-009 770, JP 51-131 875; BE 770,911, BE 859,415, BE 830,403; Patent applications EP 477 819, EP 454 330, EP 526 434.
- the benzimidazolones can be prepared according to the process described in Eur. J. Med. Chem., 1981, 16 (4), 321-326, as follows.
- the compounds (VI) can also be obtained by heating the compounds (IV) and (V) in 2-ethoxyethanol (J. Chem. Soc. 1960, 314-318) or in ethylene glycol in the presence of sodium acetate or in 1,2,3,4-tetramethylbenzene or in Decaline®.
- the compounds (VI) in which R'3 is a (C1-C8) alkylene group substituted by a (C1-C4) alkoxy can be prepared by reaction of a compound (VI) in which the substituent R'3 is a ( C1-C8) alkyl substituted by hydroxy with a halo (C1-C4) alkyl, in the presence of a metal hydride such as sodium hydride for example, in an anhydrous solvent such as DMF or THF.
- a metal hydride such as sodium hydride for example
- the reduction can be catalytic using for example palladium on carbon or Raney® nickel, or chemical using iron, zinc or tin under acidic conditions (J. Chem. Soc. 1960, 314).
- the compounds of formula (VIII) and / or (VIII ') are cyclized to benzimidazol-2-one (IX) by heating with sodium ethylate.
- the compounds (IX) can also be obtained by reaction of a compound of formula (VII) with urea according to the method described in J. Chem. Soc. 1960, 314 or with 1,1'-carbonyldiimidazole according to a process described in European patent 92391.
- the compounds of formula (II) carrying certain substituents R'1, R'2 on their benzene part are used as precursors for the preparation of compounds of formula (II) carrying other substituents R'1, R'2.
- the compounds of formula (IV) are known or can be prepared by known methods.
- the differently substituted cyclohexylamines are prepared according to J. Org. Chem., 1962, 27 , 3568-3572.
- the benzenesulfonyl halides (III) are prepared by known methods.
- 4-dimethylaminobenzenesulfonyl chloride is prepared according to CN Sukenik et al., J. Amer. Chem. Soc., 1977, 99 , 851-858.
- the benzenesulfonyl (III) halides in which the substituent R'6 is a dimethylamino group are known or prepared by known methods;
- p-Benzyloxybenzenesulfonyl chloride is prepared according to European patent application EP 229 566.
- Alkoxybenzenesulfonyl chloride is prepared from sodium alkoxybenzenesulfonate, itself prepared by the action of an alkyl halide on sodium hydroxybenzenesulfonate.
- haloalkoxybenzenesulfonyl chlorides can be prepared according to US Pat. No. 2,540,057.
- the benzenesulfonyl halides (III) in which the substituent R'6 represents an alkoxycarbonyl, a phenoxycarbonyl, a benzyloxycarbonyl, an alkylthio, a phenylthio, a benzylthio or a group SR7, R7 being as defined for (I), are prepared according to (I) Collar. Czechoslov. Chem. Commun., 1984, 49 , 1184, from an aniline derivative substituted with the same group R'6, said aniline derivative being itself obtained from the corresponding nitro derivative.
- Nitrobenzoic acid derivatives are known; by a suitable esterification reaction of this acid, the corresponding alkyl and phenyl esters are obtained.
- 2,4-dimethoxybenzene-1,5-disulfonyl dichloride is described in R.J.W. Cremlyn, J. Chem. Soc. C, 1969, 1341-1345.
- the corresponding benzenesulfonyl halides are obtained according to Col. Czechoslov. Chem. Commun., 1984, 49 , 1184, from aniline derivatives substituted by the same group, said aniline derivatives themselves being obtained from corresponding nitro derivatives.
- 4- (morpholin-4-yl) benzenesulfonyl chloride is prepared according to RJ Cremlyn et al., In Phosphor. Sulfur. Silicon., 1992, 73 (1-4), 107-120.
- the compounds according to the invention (I) can be prepared starting from a precursor of formula (I ') substituted by a group R'1, R' 2, R ' 3, R'5 and / or R'6 called a precursor group of R1, R2, R3, R5 and / or R6 using methods known to those skilled in the art.
- the compounds (I) in which R1 and / or R6 is a hydroxy can be obtained by catalytic hydrogenation, for example in the presence of palladium on carbon, of a compound of formula (I ') in which R'1 and / or R '6 is a benzyloxy.
- These compounds can also be prepared from analogous compounds of formula (I ') in which R'1 and / or R'6 represents an amino group using the method described in J. Org. Chem., 1977, 42 , 2053.
- the compounds (I ') in which R'1 and / or R'6 represents a hydroxy also make it possible to prepare compounds (I) in which R1 and / or R6 is a (C1-C7) alkoxy by the action of a halide of C1-C7 alkyl in the presence of a base such as a metal hydride or an alkaline or alkaline earth carbonate such as K2CO3 or Cs2CO3 in a solvent such as THF or DMF.
- R1 and / or R6 represents a formyloxy or respectively a (C1-C7) alkylcarbonyloxy or a benzoyloxy are obtained by the action of formic acid in dicyclohexylcarbodiimide (Huang et al., J. Chem Res. (S), 1991, 292-293) or respectively of an acid halide or an anhydride on a compound (I ') in which R'1 and / or R'6 is hydroxy.
- R6 is an OR7 group
- R7 representing a ⁇ -carbamoyl (C1-C7) alkyl which is free or substituted by one or two C1-C7 alkyls
- R'6 represents an OR''6 group
- R''6 representing a ⁇ -carboxy (C1-C7) alkyl esterified by a C1-C7 alkyl. This preparation is carried out in a conventional manner for those skilled in the art by the action of a correctly chosen amine.
- the compounds of formula (I) can be prepared in which R6 represents an amino group substituted by a benzyl, itself optionally substituted, or by a C3-C8 alkene, by the action of a benzyl chloride or of a chloroalkene in C3-C8, on a compound of formula (I ') in which R'6 is an amino group or (C1-C7) alkylamino.
- the compounds of formula (I) in which R6 represents a ⁇ 3-pyrrolin-1-yl group are prepared by the action, under an inert atmosphere, of cis-1,4-dichlorobut-2-ene on the compounds of formula (I ') in which R'6 is an amino group in the presence of a base such as triethylamine.
- the compounds of formula (I) in which R6 is a pyrrolidin-1-yl group are then prepared by hydrogenation.
- reaction of cis-1,4-dichlorobut-2-ene with the compounds (I ') in which R'6 is an amino group can also be carried out in air in the presence of a base such as Na2CO3 and leads , under these conditions, to the formation of a mixture of a compound of formula (I) in which R6 represents a group ⁇ 3-pyrrolin-1-yl and of a compound of formula (I) in which R6 represents a group pyrrol-1-yl which can be separated by chromatography.
- the compounds of formula (I) in which R6 represents an isoindolin-2-yl group are prepared by the action of ⁇ , ⁇ '-dibromo-o-xylene on the compounds of formula (I ') in which R'6 is an amino group in the presence of a base such as triethylamine, and in a solvent such as dimethylformamide at reflux.
- R'1 and / or R'6 represents an amino
- nitrosation can also be carried out, for example in the presence of nitrous acid or sodium nitrite to prepare a compound (I ') in which R'1 and / or R'6 represents a diazonium salt; by reactions known to those skilled in the art, the compounds (I) according to the invention are then accessed in which R1 and / or R6 is a cyano, a halo or a Cio-C7 thioalkyl.
- R6 represents a (C1-C7) alkoxycarbonyl
- R6 represents a (C1-C7) alkoxycarbonyl
- the compounds of formula (I ') in which R'6 is a carboxy can be used to obtain the compounds of formula (I) in which R6 is a group -CONR19R20 by action of a compound of formula HNR19R20, in the presence of BOP and an amine such as diisopropylethylamine.
- the compounds of formula (I) in which R6 is a group -CONHCR10R23COR12 are prepared from compounds of formula (I ') in which R'6 represents either a -COCl group or a phenoxycarbonyl group, by action of H2NCR10R23COR12. They can also be prepared from compounds of formula (I ') in which R'6 is a carboxy by reaction with a compound H2NCR10R23COR12 in the presence of BOP and an amine such as diisopropylethylamine.
- a compound (I) in which R6 is a thiocarbamoyl can be prepared by reacting the Lawesson reagent with a compound (I) in which R6 is the corresponding carbamoyl.
- a compound (I ') in which R'6 is a nitro group makes it possible to obtain by catalytic hydrogenation, for example in the presence of platinum oxide, Raney® nickel or palladium on carbon, or by chemical reduction, by example in the presence of tin or iron in an acid medium, a compound (I) in which R6 is an amino group; other compounds in which the amino group is substituted can then be prepared using reactions well known to those skilled in the art.
- R6 represents a group -NR8R9, R9 being a (C1-C 7) alkylcarbonyl, a formyl, a (C3-C7) cycloalkylcarbonyl, an optionally substituted benzoyl, a pyridylcarbonyl, a methylpyridylcarbonyl, a thienylcarbonyl, are obtained by the action of formic acid in acetic anhydride or of the appropriate anhydride or of the appropriate acid chloride on a compound (I ') in which R'6 is an amino group, in the presence of an amine like triethylamine.
- the acid chloride R11R27NCR10R23COCl is made to act on a compound of formula (I ') in which R'6 is a group -NHR8 to prepare a compound of formula (I) in which R6 is a group -NR8COCR10R23NR11R27 .
- a compound (I) in which R6 is a (C1-C7) alkylsulfonamido group or respectively a benzylsulfonamido or a group -NHSO2Ar is obtained by the action of a halide of (C1-C7) alkylsulfonyl or respectively a benzylsulfonyl halide or an ArSO2Cl compound on a compound (I ') in which R'6 is an amino group.
- the compounds of formula (I ') in which R'6 is an amino group are also useful for the preparation of compounds in which this amino group is substituted by a (CH2) t -COR12 group.
- a compound of formula Hal- (CH2) t -COOAlk in which Hal represents a halogen, for example bromine and Alk represents a C1-C7 alkyl is made to act on (I ′) in the presence of cuprous chloride; where appropriate, the ester thus obtained is transformed into an acid or an amide.
- an anhydride such as succinic anhydride or glutaric anhydride
- R'6 is an amino
- the acid thus obtained is converted into an ester or an amide.
- the compounds of formula (I) in which R6 is an amino group substituted by a group CR10R23COR12 are prepared by the action of a compound of formula Hal-CR10R23COR12 on the corresponding compounds (I ') in which the substituent R '6 is an amino.
- a compound of formula (I) is prepared in which R6 is a ureido or a thiouréido ; by action on such a compound of formula (I ') of a correctly substituted aniline or of a correctly substituted C1-C7 mono or dialkylamine, a compound of formula (I) is prepared in which R6 is an N'-phenylureido correctly substituted, N'-alkyl reflexido or N ', N'-dialkyl negligenceido in which the alkyl is C en-C7 correctly substituted.
- the compounds (I) in which R6 is a guanidino group which is unsubstituted or substituted once or twice by C1-C alk alkyl, phenyl or benzyl can be prepared from the compounds (I ') in which R'6 is a phenoxyamido group by the action of cyanamide or one of its derivatives correctly substituted on nitrogen.
- a compound (I) in which R6 is a sulfamoyl group substituted by R21R22 is prepared by the action of a compound HNR21R22 on a compound (I ') in which R'6 is a halosulfonyl group.
- the affinity of the compounds according to the invention for vasopressin receptors was determined in vitro using the method described in CJ Lynch et al., J. Biol. Chem., 1985, 260 (5), 2844-2851. This method consists in studying the displacement of tritiated vasopressin attached to the V1 sites of rat liver membranes.
- the 50% inhibitory concentrations (CI50) of the binding of tritiated vasopressin of the compounds according to the invention are low, ranging up to 10 ⁇ 7M.
- the affinity of the compounds (I) according to the invention for the V2 receptors was measured on a membrane preparation of beef kidney according to a method adapted from P. Crause et al., Molecular and Cellular Endocrinology, 1982, 28 , 529- 541 and FL Stassen et al., J. Pharmacol. Exp. Ther., 1982, 223 , 50-54.
- the compounds according to the invention inhibit the binding of tritiated arginine vasopressin to the receptors of the membrane preparation.
- the CI50 of the compounds according to the invention are low, ranging up to 10 ⁇ 9M.
- the antagonist activity of the V2 receptors of the compounds according to the invention has been shown by the assay for the adenylate cyclase activity performed according to a method adapted from M. Laburthe et al., Molecular Pharmacol., 1986, 29 , 23- 27.
- a membrane preparation of beef kidney is used and each product is incubated for 10 minutes at 37 ° C, alone or in the presence of AVP (arginine vasopressin) at a concentration of 3.10 ⁇ 8 M.
- Cyclic AMP cyclic adenosine monophosphate
- the concentration inhibiting by 50% is determined.
- the CI50 determined are of the order of 10 ⁇ 7M, going up to 10 ⁇ 8M.
- the agonist or antagonist activity of the vasopressin receptors of the compounds according to the invention, administered orally, is evaluated in rats (OFA strain, Sprague-Dawley) in water overload, treated with vasopressin.
- the antagonistic activity of the compounds according to the invention was also evaluated in the normally hydrated rat (OFA strain, Sprague-Dawley) according to the technique described in Br. J. Pharmacol., 1992, 105 , 787-791. The diuretic effect was observed for certain compounds at a dose of 10 mg / kg.
- the affinity of the compounds (I) according to the invention for the oxytocin receptors was determined in vitro by displacement of a radioiodinated analog of oxytocin attached to the receptors of a membrane preparation of mammary glands of pregnant rats using a technique similar to that described by J. Eland et al. in Eur. J. Pharmacol., 1987, 147 , 197-207.
- the CI50 of the compounds according to the invention reach 10 ⁇ 8M.
- the compounds according to the invention are active after administration by various routes, in particular by oral route.
- the compounds according to the invention can be used in the treatment or prevention of various vasopressin-dependent or oxytocin-dependent conditions, cardiovascular conditions, such as hypertension, pulmonary hypertension, heart failure, myocardial infarction , or coronary vasospasm, in particular in smokers, unstable angina and PTCA (percutaneous transluminal coronary angioplasty), cardiac ischemia, hemostasis disorders, in particular hemophilia, Von Willebrand syndrome; affections of the central nervous system, migraine, cerebral vasospasm, cerebral hemorrhage, cerebral edemas, depression, anxiety, psychotic states, memory disorders for example; conditions of the renal system such as edema, renal vasospasm, necrosis of the renal cortex, hyponatremia, hypokalemia, Schwartz Bartter syndrome; disorders of the gastric system such as gastric vasospasm, hepatocirrhosis, ulcers, vomiting pathology, for example nausea including nausea due to chemotherapy, motion sickness, or
- the compounds according to the invention can also be used in the treatment of disorders of the sexual behavior; in women, the compounds according to the invention can be used to treat dysmenorrhea or premature labor.
- the compounds according to the invention can also be used in the treatment of small cell lung cancers, hyponatraemic encephalopathies, Raynaud's disease, pulmonary syndrome, glaucoma and in post-operative treatments, in particular after abdominal surgery.
- the present invention also relates to pharmaceutical compositions containing an effective dose of a compound according to the invention or a pharmaceutically acceptable salt thereof and suitable excipients.
- Said excipients are chosen according to the pharmaceutical form and the desired mode of administration.
- compositions of the present invention for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, intratracheal, intranasal, transdermal or rectal administration, the active ingredients of formula (I) above, or their optional salts, can be administered in unit administration forms, in mixture with conventional pharmaceutical carriers, to animals and humans for the prophylaxis or treatment of the above disorders or diseases.
- Suitable unit administration forms include oral forms such as tablets, capsules, powders, granules and oral solutions or suspensions, sublingual, buccal, intratracheal, intranasal administration forms, subcutaneous, intramuscular or intravenous administration and forms of rectal administration.
- the compounds according to the invention can be used in creams, ointments or lotions.
- the dose of active principle can vary between 0.01 and 50 mg per kg of body weight per day.
- Each unit dose may contain from 0.5 to 1000 mg, preferably from 1 to 500 mg, of active ingredients in combination with a pharmaceutical carrier. This unit dose can be administered 1 to 5 times a day so as to administer a daily dosage of 0.5 to 5000 mg, preferably 1 to 2500 mg.
- the main active ingredient is mixed with a pharmaceutical vehicle such as gelatin, starch, lactose, magnesium stearate, talc, gum arabic or the like.
- a pharmaceutical vehicle such as gelatin, starch, lactose, magnesium stearate, talc, gum arabic or the like.
- the tablets can be coated with sucrose, a cellulose derivative, or other suitable materials or they can be treated in such a way that they have a prolonged or delayed activity and that they continuously release a quantity predetermined active ingredient.
- a preparation in capsules is obtained by mixing the active ingredient with a diluent and by pouring the mixture obtained into soft or hard capsules.
- a preparation in the form of a syrup or elixir or for administration in the form of drops may contain the active ingredient together with a sweetener, preferably calorie-free, methylparaben and propylparaben as an antiseptic, as well as a flavoring agent and an appropriate dye.
- a sweetener preferably calorie-free, methylparaben and propylparaben as an antiseptic, as well as a flavoring agent and an appropriate dye.
- Water dispersible powders or granules may contain the active ingredient in admixture with dispersing agents or wetting agents, or suspending agents, such as polyvinylpyrrolidone, as well as with sweeteners or correctors taste.
- Suppositories are used for rectal administration which are prepared with binders that melt at rectal temperature, for example cocoa butter or polyethylene glycols.
- aqueous suspensions, isotonic saline solutions or sterile injectable solutions which contain pharmacologically compatible dispersing agents and / or wetting agents, for example propylene glycol or butylene glycol.
- the active principle can also be formulated in the form of microcapsules, optionally with one or more carriers or additives.
- compositions of the present invention may contain, in addition to the products of formula (I) above or one of their pharmaceutically acceptable salts, other active ingredients which may be useful in the treatment of the disorders or diseases indicated above. above.
- the present invention also relates to pharmaceutical compositions containing several active principles in combination, one of which is a compound according to the invention.
- compositions can be prepared containing a compound according to the invention combined with a compound acting on the renin-angiotensin system such as an inhibitor of the converting enzyme, an angiotensin II antagonist , a renin inhibitor. It is also possible to combine a compound according to the invention, for example, with a peripheral vasodilator, a calcium channel blocker, a beta-blocker, an alpha-1-blocker or a diuretic. Such compositions will be useful in particular in the treatment of hypertension or heart failure.
- This compound is prepared according to the procedures described in Preparation 10 steps D, E then F from 17.4 g of the compound obtained in the previous step. 11.5 g of the expected product are obtained, mp 118-120 ° C.
- This compound is prepared according to the procedure described in EXAMPLE 33 from 0.6 g of 5-ethoxy-1,3-dihydro-3- [2- (morpholin-4-yl) ethyl] -2 H - benzimidazol-2-one. 0.75 g of the expected product is obtained after crystallization from ether, mp 146-149 ° C.
- a mixture of 0.72 g of the compound obtained in the preceding step, 0.17 g of dimethylamine hydrochloride, 2 ml of DIPEA, 0.9 g of BOP and 20 ml of DCM is left stirring at AT for 3 hours at RT.
- the reaction mixture is concentrated under vacuum, the residue is extracted with AcOEt, washed with water, with a 1N HCl solution, with a 1N NaOH solution, dried over Na2SO4 and the solvent evaporated under vacuum.
- the reaction mixture is evaporated under vacuum, the residue is extracted with AcOEt, washed with a 1N NaOH solution, extracted with AcOEt, washed with a 6N HCl solution, the acidic aqueous phase is made alkaline by adding 2N NaOH, extracted with AcOEt, dried over Na2SO4 and the solvent evaporated under vacuum.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9309403A FR2708608B1 (fr) | 1993-07-30 | 1993-07-30 | Dérivés de N-sulfonylbenzimidazolone, leur préparation, les compositions pharmaceutiques en contenant. |
FR9309403 | 1993-07-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0636614A1 true EP0636614A1 (fr) | 1995-02-01 |
Family
ID=9449793
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP94401736A Withdrawn EP0636614A1 (fr) | 1993-07-30 | 1994-07-28 | Dérivés de 1-benzènesulfonyl-1,3-dihydro-2H-benzimidazol-2-one, leur préparation, les compositions pharmaceutiques en contenant |
Country Status (16)
Country | Link |
---|---|
US (1) | US5585394A (no) |
EP (1) | EP0636614A1 (no) |
JP (1) | JPH07215947A (no) |
KR (1) | KR950003275A (no) |
CN (1) | CN1106804A (no) |
AU (1) | AU679535B2 (no) |
CA (1) | CA2129214A1 (no) |
FI (1) | FI943571A (no) |
FR (1) | FR2708608B1 (no) |
HU (1) | HUT67801A (no) |
IL (1) | IL110481A0 (no) |
NO (1) | NO304374B1 (no) |
NZ (1) | NZ264119A (no) |
RU (1) | RU2135477C1 (no) |
TW (1) | TW368500B (no) |
ZA (1) | ZA945655B (no) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996036611A1 (en) * | 1995-05-19 | 1996-11-21 | Chiroscience Limited | 3,4-disubstituted-phenylsulphonamides and their therapeutic use |
WO1997040035A1 (en) * | 1996-04-19 | 1997-10-30 | Neurosearch A/S | 1-(4-piperidyl)-benzimidazoles having neurotrophic activity |
US5756497A (en) * | 1996-03-01 | 1998-05-26 | Merck & Co., Inc. | Tocolytic oxytocin receptor antagonists |
WO2005009996A1 (en) * | 2003-07-23 | 2005-02-03 | Wyeth | Sulfonyldihydro- benzimidazolone compounds as 5-hydroxytryptamine-6 ligands |
EP1598339A1 (en) * | 2001-04-18 | 2005-11-23 | Euro-Celtique S.A. | 1-(4-amino-cyclohexyl)-1,3-dihydro-2h-benzimidazole-2-one derivatives and related compounds as nociceptin analogs and orl1 ligands for the treatment of pain |
WO2010063402A1 (de) * | 2008-12-06 | 2010-06-10 | Bayer Schering Pharma Aktiengesellschaft | Substituierte benzyl- und phenylsulfonyltriazolone und ihre verwendung |
Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19929076A1 (de) * | 1999-06-25 | 2000-12-28 | Aventis Pharma Gmbh | Indanylsubstituierte Benzolcarbonamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
JP4710140B2 (ja) * | 2000-01-20 | 2011-06-29 | 東レ・ファインケミカル株式会社 | ピロリン誘導体の製造法 |
KR20030007575A (ko) * | 2000-05-03 | 2003-01-23 | 수캄포 아게 | 안압 강하제 |
US6653478B2 (en) | 2000-10-27 | 2003-11-25 | Ortho-Mcneil Pharmaceutical, Inc. | Substituted benzimidazol-2-ones as vasopressin receptor antagonists and neuropeptide Y modulators |
CA2532076A1 (en) * | 2003-07-23 | 2005-02-03 | Wyeth | Sulfonyldihydroimid- azopyridinone compounds as 5-hydroxytryptamine-6 ligands |
EP1750862B1 (en) | 2004-06-04 | 2011-01-05 | Teva Pharmaceutical Industries Ltd. | Pharmaceutical composition containing irbesartan |
US8138342B2 (en) * | 2004-10-12 | 2012-03-20 | High Point Pharmacueticals, LLC | 11β-hydroxysteroid dehydrogenase type 1 active spiro compounds |
EP1948190A2 (en) * | 2005-11-01 | 2008-07-30 | Transtech Pharma | Pharmaceutical use of substituted amides |
KR20080069189A (ko) * | 2005-11-01 | 2008-07-25 | 트랜스테크 파르마, 인크. | 치환된 아미드의 약학적 사용 |
US20100168083A1 (en) * | 2006-03-21 | 2010-07-01 | Soren Ebdrup | Adamantane derivatives for the treatment of the metabolic syndrome |
AU2007236049A1 (en) | 2006-04-07 | 2007-10-18 | High Point Pharmaceuticals, Llc | 11beta-hydroxysteroid dehydrogenase type 1 active compounds |
DE102006024024A1 (de) * | 2006-05-23 | 2007-11-29 | Bayer Healthcare Aktiengesellschaft | Substituierte Arylimidazolone und -triazolone sowie ihre Verwendung |
EP2038255A2 (en) * | 2006-06-16 | 2009-03-25 | High Point Pharmaceuticals, LLC | Pharmaceutical use of substituted piperidine carboxamides |
EP1878721A1 (en) * | 2006-07-13 | 2008-01-16 | Novo Nordisk A/S | 4-Piperidylbenzamides as 11-beta-hydroxysteroid dehydrogenase type 1 inhibitors |
US8048908B2 (en) * | 2006-07-13 | 2011-11-01 | High Point Pharmaceuticals, Llc | 11β-hydroxysteroid dehydrogenase type 1 active compounds |
EP2061769A1 (en) * | 2006-08-26 | 2009-05-27 | Abbott GmbH & Co. KG | Substituted benzimidazolone derivatives, medicaments comprising them and their use |
EA016951B1 (ru) | 2007-02-23 | 2012-08-30 | ХАЙ ПОЙНТ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи | N-АДАМАНТИЛБЕНЗАМИДЫ В КАЧЕСТВЕ ИНГИБИТОРОВ 11-β-ГИДРОКСИСТЕРОИДДЕГИДРОГЕНАЗЫ |
EP2125704A1 (en) * | 2007-02-23 | 2009-12-02 | High Point Pharmaceuticals, LLC | N-adamantyl benzamides as inhibitors of 11-beta-hydroxysteroid dehydrogenase |
WO2008101907A2 (en) | 2007-02-23 | 2008-08-28 | High Point Pharmaceuticals, Llc | N-adamantyl benzamides as inhibitors of 11-beta-hydroxysteroid dehydrogenase |
US20110003852A1 (en) * | 2007-02-23 | 2011-01-06 | Soren Ebdrup | N-adamantyl benzamides as inhibitors of 11-beta-hydroxysteroid dehydrogenase |
JP2010520864A (ja) * | 2007-03-09 | 2010-06-17 | ハイ ポイント ファーマシューティカルズ,リミティド ライアビリティ カンパニー | ヒドロキシステロイドデヒドロゲナーゼインヒビターとしてのインドール−及びベンズイミダゾールアミド類 |
CN101677562A (zh) * | 2007-04-11 | 2010-03-24 | 高点制药有限责任公司 | 新化合物 |
JP2010526777A (ja) * | 2007-04-24 | 2010-08-05 | ハイ ポイント ファーマシューティカルズ,リミティド ライアビリティ カンパニー | 置換アミドの医薬用途 |
US8927549B2 (en) * | 2008-11-21 | 2015-01-06 | High Point Pharmaceuticals, Llc | Adamantyl benzamide derivatives |
DE102010001064A1 (de) * | 2009-03-18 | 2010-09-23 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 2-Acetamido-5-Aryl-1,2,4-triazolone und deren Verwendung |
LT2539326T (lt) | 2010-02-27 | 2017-08-10 | Bayer Intellectual Property Gmbh | Sujungti bisariliniai ariltriazolonai ir jų panaudojimas |
DE102010040187A1 (de) | 2010-09-02 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Substituierte N-Phenethyl-triazolonacetamide und ihre Verwendung |
DE102010040924A1 (de) | 2010-09-16 | 2012-03-22 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Phenylacet- und Phenylpropanamide und ihre Verwendung |
JP6623220B2 (ja) | 2014-11-03 | 2019-12-18 | バイエル ファーマ アクチエンゲゼルシャフト | ヒドロキシアルキル置換フェニルトリアゾール誘導体およびその使用 |
US9988367B2 (en) | 2016-05-03 | 2018-06-05 | Bayer Pharma Aktiengesellschaft | Amide-substituted pyridinyltriazole derivatives and uses thereof |
WO2024050312A2 (en) * | 2022-08-29 | 2024-03-07 | The Broad Institute, Inc. | T-type voltage-gated calcium channel potentiators |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0324988A1 (de) * | 1987-12-30 | 1989-07-26 | CHINOIN Gyogyszer és Vegyészeti Termékek Gyára RT. | 4-Chlor-3-sulfamoyl-benzoesäure-hydrazide, Verfahren zu ihrer Herstellung, diese Verbindungen enthaltende Arzneimittelpräparate und Verwendung der neuen Verbindungen zur Herstellung von diuretischen und salzentziehend wirkenden Arzneimittelpräparaten |
EP0470514A1 (en) * | 1990-08-07 | 1992-02-12 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivatives and pharmaceutical composition containing the same |
EP0526348A1 (fr) * | 1991-08-02 | 1993-02-03 | Sanofi | Dérivés d'indoline portant une fonction amidique, leur préparation, les compositions pharmaceutiques en contenant |
WO1993015051A1 (fr) * | 1992-01-30 | 1993-08-05 | Elf Sanofi | Derives du n-sulfonyl-2-oxoindole ayant une affinite pour les recepteurs de la vasopressine et/ou de l'ocytocine |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3405136A (en) * | 1964-09-15 | 1968-10-08 | Upjohn Co | 1-phenylsulfonyl-2-benzimidazo-linones and 1-phenylsulfonyl-2-benzimidazolinethiones |
BE792402A (fr) * | 1971-12-07 | 1973-06-07 | Ciba Geigy | Composes heterocycliques azotes et medicaments anthelminthiqueset antimicrobiens qui en contiennent |
CH634307A5 (de) * | 1977-04-12 | 1983-01-31 | Ciba Geigy Ag | Anthelmintisch wirkende benzimidazolderivate, verfahren zu ihrer herstellung und mittel enthaltend diese wirkstoffe. |
US5338755A (en) * | 1990-07-31 | 1994-08-16 | Elf Sanofi | N-sulfonylindoline derivatives, their preparation and the pharmaceutical compositions in which they are present |
-
1993
- 1993-07-30 FR FR9309403A patent/FR2708608B1/fr not_active Expired - Fee Related
-
1994
- 1994-07-28 EP EP94401736A patent/EP0636614A1/fr not_active Withdrawn
- 1994-07-28 NZ NZ264119A patent/NZ264119A/en unknown
- 1994-07-28 IL IL11048194A patent/IL110481A0/xx unknown
- 1994-07-29 TW TW083107082A patent/TW368500B/zh active
- 1994-07-29 US US08/282,547 patent/US5585394A/en not_active Expired - Fee Related
- 1994-07-29 AU AU68788/94A patent/AU679535B2/en not_active Ceased
- 1994-07-29 RU RU94027577A patent/RU2135477C1/ru active
- 1994-07-29 ZA ZA945655A patent/ZA945655B/xx unknown
- 1994-07-29 CA CA002129214A patent/CA2129214A1/en not_active Abandoned
- 1994-07-29 FI FI943571A patent/FI943571A/fi unknown
- 1994-07-29 NO NO942835A patent/NO304374B1/no not_active IP Right Cessation
- 1994-07-29 HU HU9402238A patent/HUT67801A/hu unknown
- 1994-07-30 CN CN94114901A patent/CN1106804A/zh active Pending
- 1994-07-30 KR KR1019940018913A patent/KR950003275A/ko not_active Application Discontinuation
- 1994-08-01 JP JP6199080A patent/JPH07215947A/ja not_active Withdrawn
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0324988A1 (de) * | 1987-12-30 | 1989-07-26 | CHINOIN Gyogyszer és Vegyészeti Termékek Gyára RT. | 4-Chlor-3-sulfamoyl-benzoesäure-hydrazide, Verfahren zu ihrer Herstellung, diese Verbindungen enthaltende Arzneimittelpräparate und Verwendung der neuen Verbindungen zur Herstellung von diuretischen und salzentziehend wirkenden Arzneimittelpräparaten |
EP0470514A1 (en) * | 1990-08-07 | 1992-02-12 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivatives and pharmaceutical composition containing the same |
EP0526348A1 (fr) * | 1991-08-02 | 1993-02-03 | Sanofi | Dérivés d'indoline portant une fonction amidique, leur préparation, les compositions pharmaceutiques en contenant |
WO1993015051A1 (fr) * | 1992-01-30 | 1993-08-05 | Elf Sanofi | Derives du n-sulfonyl-2-oxoindole ayant une affinite pour les recepteurs de la vasopressine et/ou de l'ocytocine |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996036611A1 (en) * | 1995-05-19 | 1996-11-21 | Chiroscience Limited | 3,4-disubstituted-phenylsulphonamides and their therapeutic use |
US5756497A (en) * | 1996-03-01 | 1998-05-26 | Merck & Co., Inc. | Tocolytic oxytocin receptor antagonists |
WO1997040035A1 (en) * | 1996-04-19 | 1997-10-30 | Neurosearch A/S | 1-(4-piperidyl)-benzimidazoles having neurotrophic activity |
US6180649B1 (en) | 1996-04-19 | 2001-01-30 | Nerosearch A/S | 1-(4-piperidyl)-benzimidazoles having neurotrophic activity |
EP1598339A1 (en) * | 2001-04-18 | 2005-11-23 | Euro-Celtique S.A. | 1-(4-amino-cyclohexyl)-1,3-dihydro-2h-benzimidazole-2-one derivatives and related compounds as nociceptin analogs and orl1 ligands for the treatment of pain |
WO2005009996A1 (en) * | 2003-07-23 | 2005-02-03 | Wyeth | Sulfonyldihydro- benzimidazolone compounds as 5-hydroxytryptamine-6 ligands |
US7544701B2 (en) * | 2003-07-23 | 2009-06-09 | Wyeth | Sulfonyldihydrobenzimidazolone compounds as 5-hydroxytryptamine-6 ligands |
WO2010063402A1 (de) * | 2008-12-06 | 2010-06-10 | Bayer Schering Pharma Aktiengesellschaft | Substituierte benzyl- und phenylsulfonyltriazolone und ihre verwendung |
Also Published As
Publication number | Publication date |
---|---|
ZA945655B (en) | 1995-03-14 |
JPH07215947A (ja) | 1995-08-15 |
FR2708608B1 (fr) | 1995-10-27 |
AU6878894A (en) | 1995-02-09 |
NO304374B1 (no) | 1998-12-07 |
NZ264119A (en) | 1996-02-27 |
FR2708608A1 (fr) | 1995-02-10 |
RU2135477C1 (ru) | 1999-08-27 |
FI943571A0 (fi) | 1994-07-29 |
HU9402238D0 (en) | 1994-09-28 |
NO942835L (no) | 1995-01-31 |
IL110481A0 (en) | 1994-10-21 |
TW368500B (en) | 1999-09-01 |
NO942835D0 (no) | 1994-07-29 |
AU679535B2 (en) | 1997-07-03 |
RU94027577A (ru) | 1996-05-27 |
FI943571A (fi) | 1995-01-31 |
CA2129214A1 (en) | 1995-01-31 |
CN1106804A (zh) | 1995-08-16 |
US5585394A (en) | 1996-12-17 |
HUT67801A (en) | 1995-05-29 |
KR950003275A (ko) | 1995-02-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0636614A1 (fr) | Dérivés de 1-benzènesulfonyl-1,3-dihydro-2H-benzimidazol-2-one, leur préparation, les compositions pharmaceutiques en contenant | |
EP0581939B1 (fr) | Derives du n-sulfonyl-2-oxoindole ayant une affinite pour les recepteurs de la vasopressine et/ou de l'ocytocine | |
EP0687251B1 (fr) | Derives de 1,3-dihydroindol-2-one substitues en 3 par un groupe azote comme agonistes et/ou antagonistes de la vasopressine et/ou de l'ocytocine | |
EP0950047B1 (fr) | Derives d'indolin-2-one, procede pour leur preparation et compositions pharmaceutiques les contenant | |
EP0636608A1 (fr) | Dérivés du 1-benzènesulfonyl-1,3-dihydro-indol-2-one, leur préparation, les compositions pharmaceutiques en contenant | |
EP0636609A1 (fr) | Dérivés du 1-benzyl-1,3-dihydro-indol-2-one, leur préparation, les compositions pharmaceutiques en contenant | |
EP0873309B1 (fr) | Derives 3-spiro-indolin-2-one comme ligands des recepteurs de la vasopressine et/ou de l'ocytocine | |
EP0454511B1 (fr) | Dérivés hétérocycliques N-substitués leur préparation, les compositions pharmaceutiques en contenant | |
EP0501892B1 (fr) | Dérivés hétérocycliques diazotés N-substitués par un groupement biphénylméthyle, leur préparation, les compositions pharmaceutiques en contenant | |
EP0694536A1 (fr) | Dérivés de 1-benzyl-1,3-dihydro-2H-benzimidazol-2-one, leur préparation, et compositions pharmaceutiques les contenant | |
EP1296976B1 (fr) | Derives de 1,3-dihydro-2h-indol-2-one et leur utilisation en tant que ligands des recepteurs v1b et v1a de l'arginine-vasopressine | |
EP1259505B1 (fr) | Derives de 1,3-dihydro-2h-indol-2-one et leur utilisation en tant que ligands des recepteurs v1b ou v1b et v1a de l'arginine-vasopressine | |
CH676120A5 (no) | ||
EP0518731A1 (fr) | Dérivés hétérocycliques de 2-acylamino-5-thiazoles substitués, leur préparation et compositions pharmaceutiques en contenant | |
CA2176668C (fr) | Nouveaux composes spiro heterocycliques, leur procede de preparation et les compositions pharmaceutiques les contenant | |
EP2188253B1 (fr) | Dérivés de l'indol-2-one disubstitués en 3, leur préparation et leur application en thérapeutique | |
EP0532410A1 (fr) | Dérivés hétérocycliques N-substitués, comme inhibiteurs de l'angiotensive II | |
EP0562936A1 (fr) | Imidazolines N-substituées par un groupement biphénylméthyle, leur préparation, les compositions pharmaceutiques en contenant | |
EP1023898A1 (fr) | Cyano-indoles en tant qu' inhibiteurs de recapture de sérotonine et ligands du récepteur 5-HT2c | |
WO2004009585A2 (fr) | Derives d'acyloxypyrrolidine et leur utilisation en tant que ligands des recepteurs v1b et v1a de avp | |
FR2659967A1 (fr) | Derives d'imidazolinone n-substitues, leur preparation, les compositions pharmaceutiques en contenant. | |
FR2665702A1 (fr) | Derives heterocycliques n-substitues, leur preparation, les compositions pharmaceutiques en contenant. | |
FR2832710A1 (fr) | Derives de 5-sulfanyl-4h-1,2,4-triazoles et leur utilisation en tant que medicaments |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU MC NL PT SE |
|
RAX | Requested extension states of the european patent have changed |
Free format text: LT PAYMENT 941028;SI PAYMENT 941028 |
|
17P | Request for examination filed |
Effective date: 19950608 |
|
17Q | First examination report despatched |
Effective date: 19980512 |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: SANOFI |
|
GRAG | Despatch of communication of intention to grant |
Free format text: ORIGINAL CODE: EPIDOS AGRA |
|
GRAG | Despatch of communication of intention to grant |
Free format text: ORIGINAL CODE: EPIDOS AGRA |
|
GRAH | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOS IGRA |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 19990723 |